HSV-2

Use of transcriptional profiling to delineate the initial response of mice to intravaginal herpes simplex virus type 2 infection.

Cherpes TL¹, Harvey SA, Phillips JM, Vicetti Miguel RD, Melan MA, Quispe Calla NE, Hendricks RL.

¹Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224, USA. cherpest@pitt.edu

 

Abstract

Intravaginal (ivag) infection of mice with herpes simplex virus type 2 (HSV-2) causes genital tissue damage, quickly followed by development of fatal encephalopathy. To delineate initial host responses generated by HSV-2 infection, here oligonucleotide microarrays compared gene expression in vaginal tissue from uninfected mice and mice 1, 2, 3, 4, 5, 6, or 7 days after ivag infection with 10(4) pfu HSV-2. While comparison of mRNA expression in uninfected and HSV-infected vaginal tissue detected few changes during the first 2 days post infection (dpi), there were 156 genes whose expression was first significantly altered 3 dpi that remained significantly modified at all later time points examined. These 156 genes were significantly enriched in canonical pathways associated with interferon (IFN) signaling, activation of IFN elements by intracellular pattern recognition receptors, and antiviral immunity induced by cytosolic RIG-like receptors. Evaluation of this gene set with the National Center for Biotechnology Information Gene and INTERFEROME databases corroborated pathway analysis, as function of most (53%) were linked to IFN-mediated host immunity. In the final set of experiments, ivag administration of the Toll-like receptor 3 agonist polyinosinic: polycytidylic acid (poly I:C) 24 h before ivag HSV-2 infection reduced the incidence of genital pathology and encephalopathy, while these poly I:C-treated mice were subsequently protected from ocular HSV-2 challenge lethal to uninfected controls. The latter results imply that the exuberant antiviral immunity produced in our experimental model is simply formed too late to prevent viral replication and dissemination, and that poly I:C-induced formation of an antiviral state protecting against primary ivag infection also permits development of HSV-specific protective immunity.

Viral Immunol. 2013 Jun;26(3):172-9. doi: 10.1089/vim.2012.0093. Epub 2013 May 2.

 http://online.liebertpub.com/doi/abs/10.1089/vim.2012.0093

Md. Rodolfo Vicetti. Ex-miembro del GII.

Cáncer y Citocinas

Chemokine-Derived Peptides: Novel Antimicrobial and Antineoplasic Agents.

 

Valdivia-Silva J1,2, Medina-Tamayo J1,2, Garcia-Zepeda EA3,4.

¹Chemokine Biology Research Laboratory, Programa Institucional de Investigación en Cancer de Mama, Mexico DF 04510, Mexico.
²Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico DF 04510, Mexico.
³Chemokine Biology Research Laboratory, Programa Institucional de Investigación en Cancer de Mama, Mexico DF 04510, Mexico. garciaze@unam.mx.
⁴Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico DF 04510, Mexico. garciaze@unam.mx.

 

Abstract

Chemokines are a burgeoning family of chemotactic cytokines displaying a broad array of functions such as regulation of homeostatic leukocyte traffic and development, as well as activating the innate immune system. Their role in controlling early and late inflammatory stages is now well recognized. An improper balance either in chemokine synthesis or chemokine receptor expression contributes to various pathological disorders making chemokines and their receptors a useful therapeutic target. Research in this area is progressing rapidly, and development of novel agents based on chemokine/ chemokine receptors antagonist functions are emerging as attractive alternative drugs. Some of these novel agents include generation of chemokine-derived peptides (CDP) with potential agonist and antagonist effects on inflammation, cancer and against bacterial infections. CDP have been generated mainly from N- and C-terminus chemokine sequences with subsequent modifications such as truncations or elongations. In this review, we present a glimpse of the different pharmacological actions reported for CDP and our current understanding regarding the potential use of CDP alone or as part of the novel therapies proposed in the treatment of microbial infections and cancer.

KEYWORDS:

cancer; chemokine; chemokine receptors; cytokines; inflammation; microbial infections; peptides

Int J Mol Sci. 2015 Jun 8;16(6):12958-12985.

http://www.mdpi.com/1422-0067/16/6/12958

Md PhD Julio Valdivia Silva. Fundador del GII

Célula Dendríticas y Medroxyprogesterona

Medroxyprogesterone acetate impairs human dendritic cell activation and function.

Quispe Calla NE¹, Ghonime MG², Cherpes TL², Vicetti Miguel RD¹.

¹Departments of Microbial Infection & Immunity and Obstetrics & Gynecology, The Ohio State University College of Medicine, Columbus, OH 43210, USA quispecalla.1@osu.edu vicettimiguel.1@osu.edu.
²Departments of Microbial Infection & Immunity and Obstetrics & Gynecology, The Ohio State University College of Medicine, Columbus, OH 43210, USA.

 

Abstract

STUDY QUESTION:

Does medroxyprogesterone acetate (MPA) impair human dendritic cell (DC) activation and function?

SUMMARY ANSWER:

In vitro MPA treatment suppressed expression of CD40 and CD80 by human primary DCs responding to Toll-like receptor 3 (TLR3) agonist stimulation (i.e. DC activation). Moreover, this MPA-mediated decrease in CD40 expression impaired DC capacity to stimulate T cell proliferation (i.e. DC function).

WHAT IS KNOWN ALREADY:

MPA is the active molecule in Depo-Provera(®) (DMPA), a commonly used injectable hormonal contraceptive (HC). Although DMPA treatment of mice prior to viral mucosal tissue infection impaired the capacity of DCs to up-regulate CD40 and CD80 and prime virus-specific T cell proliferation, neither DC activation marker expression nor the ability of DCs to promote T cell proliferation were affected by in vitro progesterone treatment of human DCs generated from peripheral blood monocytes.

STUDY DESIGN, SIZE, DURATION:

This cross-sectional study examined MPA-mediated effects on the activation and function of human primary untouched peripheral blood DCs.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Human DCs isolated from peripheral blood mononuclear cells by negative immunomagnetic selection were incubated for 24 h with various concentrations of MPA. After an additional 24 h incubation with the TLR3 agonist polyinosinic:polycytidylic acid (poly I:C), flow cytometry was used to evaluate DC phenotype (i.e. expression of CD40, CD80, CD86, and HLA-DR). In separate experiments, primary untouched human DCs were sequentially MPA-treated, poly I:C-activated, and incubated for 7 days with fluorescently labeled naïve allogeneic T cells. Flow cytometry was then used to quantify allogeneic T cell proliferation.

MAIN RESULTS AND THE ROLE OF CHANCE:

Several pharmacologically relevant concentrations of MPA dramatically reduced CD40 and CD80 expression in human primary DCs responding to the immunostimulant poly I:C. In addition, MPA-treated DCs displayed a reduced capacity to promote allogeneic CD4(+) and CD8(+) T cell proliferation. In other DC: T cell co-cultures, the addition of antibody blocking the CD40-CD154 (CD40L) interaction mirrored the decreased T cell proliferation produced by MPA treatment, while addition of recombinant soluble CD154 restored the capacity of MPA-treated DCs to induce T cell proliferation to levels produced by non-MPA-treated controls.

LIMITATIONS, REASON FOR CAUTION:

While our results newly reveal that pharmacologically relevant MPA concentrations suppress human DC function in vitro, additional research is needed to learn if DMPA similarly inhibits DC maturation and function in the human female genital tract.

WIDER IMPLICATIONS OF THE FINDINGS:

Identification of a mechanism by which MPA impairs human DC activation and function increases the biological plausibility for the relationships currently suspected between DMPA use and enhanced susceptibility to genital tract infection.

STUDY FUNDING/COMPETING INTERESTS:

Funding provided by the NIH (grant R01HD072663) and The Ohio State University College of Medicine. The authors have no conflicts of interest to declare.
© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

KEYWORDS:

T cell proliferation; costimulatory molecule expression; dendritic cell activation; medroxyprogesterone acetate

Hum Reprod. 2015 May;30(5):1169-77. doi: 10.1093/humrep/dev035. Epub 2015 Mar 3.

http://humrep.oxfordjournals.org/content/30/5/1169.long

Md. Nirk Quispe. Past-president del GII.
Md. Rodolfo Vicetti. Ex-miembro del GII.

EGFR e Inmunoterapia

Immune biomarkers of anti-EGFR monoclonal antibody therapy.

Trivedi S¹, Concha-Benavente F², Srivastava RM¹, Jie HB¹, Gibson SP¹, Schmitt NC¹, Ferris RL³.

¹Department of Otolaryngology, University of Pittsburgh School of Medicine.
²Department of Immunology, University of Pittsburgh.
³Department of Otolaryngology, University of Pittsburgh School of Medicine Department of Immunology, University of Pittsburgh Cancer Immunology Program, University of Pittsburgh Cancer Institute, Pittsburgh, USA ferrrl@upmc.edu.

 

Abstract

The tumor antigen (TA)-targeted monoclonal antibodies (mAb) cetuximab and panitumumab target the human epidermal growth factor receptor and have been integrated into treatment regimens for advanced squamous cell carcinoma of the head and neck (SCCHN). The therapeutic efficacy of these mAbs has been found to be enhanced when combined with radiotherapy and chemotherapy. However, clinical trials indicate that these findings are limited to fewer than 20% of treated patients. Therefore, identifying patients who are likely to benefit from these agents is crucial to improving therapeutic strategies. Interestingly, it has been noted that TA-targeted mAbs mediate their effects by contributing to cell-mediated cytotoxicity in addition to inhibition of downstream signaling pathways. Here, we describe the potential immunogenic mechanisms underlying these clinical findings, their role in the varied clinical response and identify the putative biomarkers of antitumor activity. We review potential immunological biomarkers that affect mAb therapy in SCCHN patients, the implications of these findings and how they translate to the clinical scenario, which are critical to improving patient selection and ultimately outcomes for patients undergoing therapy.
© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

KEYWORDS:

EGFR; head and neck cancer; immune biomarkers; monoclonal antibodies

Ann Oncol. 2015 Jan;26(1):40-7. doi: 10.1093/annonc/mdu156. Epub 2014 Jul 4.

http://annonc.oxfordjournals.org/content/26/1/40.long

Md. PhD. Fernando Concha. Ex-miembro del GII

Enterovirus e Infecciones Respiratorias

Non-rhinovirus enteroviruses associated with respiratory infections in Peru (2005-2010).

Huaman JL1, Carrion G, Ampuero JS, Gomez J, Ocaña V, Paz I, Gomez E, Chavez E, Sarmiento F, Pozo E, Laguna-Torres VA, Halsey ES.

¹US Naval Medical Research Unit No, 6, Lima, Peru. jose.huaman@med.navy.mil.

 

Abstract

BACKGROUND:

Enteroviruses (EVs) are a common cause of respiratory tract infections and are classified into seven species (EVA-D and rhinoviruses [RHVs] A-C) with more than 200 different serotypes. Little is known about the role of non-RHV EVs in respiratory infections in South America. The aim of this study was to describe the epidemiology of non-RHV EVs detected in patients with influenza-like illness enrolled in a passive surveillance network in Peru.

METHODS:

Throat swabs and epidemiological data were collected from participants after obtaining verbal consent. Viral isolation was performed in cell culture and identified by immunofluorescence assay. Serotype identification of EV isolates was performed using commercial monoclonal antibodies. Identification of non-serotypeable isolations was carried out by reverse transcriptase-PCR, followed by sequencing.

RESULTS:

Between 2005 and 2010, 24,239 samples were analyzed, and 9,973 (41.1%) possessed at least one respiratory virus. EVs were found in 175 samples (0.7%). Our results revealed a clear predominance of EVB species, 90.9% (159/175). No EVDs were isolated. The mean and median ages of EV-positive subjects were 9.1 and 4.0 years, respectively, much younger than the population sampled, 17.6 and 12.0 years. Sixteen serotypes were identified, four EVA, 11 EVB, and one EVC species. The most common serotypes were coxsackievirus B1, coxsackievirus B2, coxsackievirus B5, and coxsackievirus B3.

CONCLUSION:

This study provides data about the serotypes of EVs circulating in Peru and sets the need for further studies.

Virol J. 2014 Sep 22;11:169. doi: 10.1186/1743-422X-11-169.

 http://www.virologyj.com/content/11/1/169

Md. Irmia Paz. Tutora del GII 

Citocinas y Depresión

C-reactive protein, interleukin-6, soluble tumor necrosis factor α receptor 2 and incident clinical depression.

Chocano-Bedoya PO¹, Mirzaei F², O'Reilly EJ³, Lucas M⁴, Okereke OI⁵, Hu FB⁶, Rimm EB⁶, Ascherio A⁶.

¹Department of Nutrition, Harvard School of Public Health, Boston, MA, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA. Electronic address: pchocano@hsph.harvard.edu.
²Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
³Department of Nutrition, Harvard School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women׳s Hospital and Harvard Medical School, Boston, MA, USA.
⁴Department of Nutrition, Harvard School of Public Health, Boston, MA, USA; Department of Social and Preventive Medicine, Laval University, Québec, Canada.
⁵Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women׳s Hospital and Harvard Medical School, Boston, MA, USA; Department of Medicine, Brigham and Women׳s Hospital and Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Brigham and Women׳s Hospital and Harvard Medical School, Boston, MA, USA.
⁶Department of Nutrition, Harvard School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women׳s Hospital and Harvard Medical School, Boston, MA, USA.

 

Abstract

BACKGROUND:

Despite an extensive literature on the role of inflammation and depression, few studies have evaluated the association between inflammatory biomarkers and depression in a prospective manner, and results are inconclusive.

METHODS:

We conducted a prospective analysis of blood levels of CRP, IL-6 and TNFα-R2 in 4756 women participating in the Nurses׳ Health Study who donated blood in 1990 and were depression-free up to 1996. Participants were followed between 1996 and 2008 for reports of clinical diagnosis depression or antidepressant use. Additionally, we conducted cross-sectional analyses for CRP, IL-6 and TNFα-R2 and antidepressant use at time of blood draw.

RESULTS:

After adjustment for body mass index, menopause status, use of anti-inflammatory drugs and other covariates, no significant associations between CRP, IL-6 and TNFα-R2 and incident depression were observed after a follow-up of 6-18 years. However, menopause status appears to modify the association between IL-6 and depression risk. In cross-sectional analyses, TNFα-R2 was associated with antidepressant use (OR=1.96, 95% CI=1.23-3.13, P-trend=0.001), but no significant associations were found for CRP and IL-6.

LIMITATIONS:

Depression diagnosis was first assessed in 1996, 6 years after blood draw. However the biomarkers have high within-person correlations with measurements 4 years apart.

CONCLUSIONS:

Blood levels of CRP, IL-6 and TNFα-R2 were not associated with incident depression over a follow-up of 6-18 years. In cross-sectional analyses, antidepressant use may be associated with higher levels of TNFα-R2 but no associations with depression or antidepressant use were observed in the prospective analysis.
Copyright © 2014 Elsevier B.V. All rights reserved.

KEYWORDS:

C-reactive protein; Depression; Inflammation; Interleukin-6; Prospective study; Soluble tumor necrosis factor – receptor 2

J Affect Disord. 2014 Jul;163:25-32. doi: 10.1016/j.jad.2014.03.023. Epub 2014 Mar 27.

http://www.sciencedirect.com/science/article/pii/S0165032714001347

Md. PhD. Patricia Chocano. Ex miembro del GII. 

Inflamación y Depresión

Inflammatory dietary pattern and risk of depression among women.

Lucas M¹, Chocano-Bedoya P², Schulze MB, Mirzaei F², O'Reilly ÉJ⁴, Okereke OI⁵, Hu FB⁶, Willett WC⁶, Ascherio A⁶.

¹Department of Nutrition, Harvard School of Public Health, MA 02115, USA; Department of Social and Preventive Medicine, Laval University, Québec G1V 2M2, Canada. Electronic address: mlucas@hsph.harvard.edu.
²Department of Nutrition, Harvard School of Public Health, MA 02115, USA.
³Department of Molecular Epidemiology, German Institute of Human Nutrition, Nuthetal 14558, Germany.
⁴Department of Nutrition, Harvard School of Public Health, MA 02115, USA; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, MA 02115, USA.
⁵Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, MA 02115, USA; Department of Epidemiology, Harvard School of Public Health, MA 02115, USA; Department of Psychiatry, Brigham and Women's Hospital and Harvard Medical School, MA 02115, USA.
⁶Department of Nutrition, Harvard School of Public Health, MA 02115, USA; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, MA 02115, USA; Department of Epidemiology, Harvard School of Public Health, MA 02115, USA.

 

Abstract

BACKGROUND:

Inflammation is considered as a mechanism leading to depression, but the association between inflammatory dietary pattern and depression risk is unknown.

METHODS:

Using reduced-rank regression, we identified a dietary pattern that was related to plasma levels of inflammatory markers (C-reactive protein, interleukin-6, tumor necrosis factor α receptor 2), and we conducted a prospective analysis of the relationship of this pattern and depression risk among participants in the Nurses' Health Study. A total of 43,685 women (aged 50-77) without depression at baseline (1996) were included and followed up until 2008. Diet information was obtained from food frequency questionnaires completed between 1984 through 2002 and computed as cumulative average of dietary intakes with a 2-year latency applied. We used a strict definition of depression that required both self-reported physician-diagnosed depression and use of antidepressants, and a broader definition that included women who reported either clinical diagnosis or antidepressant use.

RESULTS:

During the 12-year follow-up, we documented 2594 incident cases of depression using the stricter definition and 6446 using the broader definition. After adjustment for body mass index and other potential confounders, relative risks comparing extreme quintiles of the inflammatory dietary pattern were 1.41 (95% confidence interval [CI], 1.22, 1.63; P-trend<.001) for the strict definition and 1.29 (95% CI, 1.18, 1.41; P-trend<.001) for the broader definition of depression.

CONCLUSIONS:

The inflammatory dietary pattern is associated with a higher depression risk. This finding suggests that chronic inflammation may underlie the association between diet and depression.
Copyright © 2013 Elsevier Inc. All rights reserved.

KEYWORDS:

C-reactive protein; Cohort; Depression; Diet pattern; Inflammatory markers; Interleukin-6; Reduced-rank regression; Tumor necrosis factor α receptor 2; Women

Brain Behav Immun. 2014 Feb;36:46-53. doi: 10.1016/j.bbi.2013.09.014. Epub 2013 Oct 1.

http://www.sciencedirect.com/science/article/pii/S0889159113004698

Md. PhD. Patricia Chocano. Ex miembro del GII.  

Dermatología e Inmunología

Las células guardianes residentes de la piel y

su papel en la respuesta inmune. Parte 1

Julio E Valdivia-Silva1,2, Monica Maya-Pasten1, Jackie Peña-Fernández1

1Chemokines Biology Research Laboratory, Instituto de Investigaciones Biomédicas, UNAM, México D.F., México.

2 Life Sciences Division, NASA Ames Research Center, Moffett Field, 94035, California, EE UU.

RESUMEN 

La piel constituye la primera barrera del sistema inmune contra potenciales agentes patógenos y nocivos externos. Evidencia importante sugiere que las células inmunológicas requieren de funciones conjuntas con los queratinocitos, para alertar y ensamblar una respuesta inmune adecuada, que incluye la formación del sistema de alerta denominado inflamosoma.

Adicionalmente, nuevos fenotipos funcionales de células presentadoras de antígenos (CPA) en la piel como las células dendríticas han demostrado tener gran importancia en ensamblar la respuesta inmune, incluso mayor que las células T circulantes.

La primera entrega de este artículo describe la funcionalidad de los queratinocitos y las células dendríticas en la piel, para en la segunda parte discriminar sus roles junto a los linfocitos T y las fallas de la regulación durante las interacciones en la formación del inflamosoma.

Palabras clave. Inmunidad de la piel, Queratinocitos, Células dendríticas, Inflamosoma.

Dermatología Peruana 01/2014; 24(1):19-26. 

http://www.dermatologia.pe/asset/uploads/archivos/publicaciones/revista/revista-24-1.pdf

Md PhD Julio Valdivia Silva. Fundador del GII

EGFR y Cáncer

EGFR-mediated tumor immunoescape: The imbalance between phosphorylated STAT1 and phosphorylated STAT3.

Concha-Benavente F¹, Srivastava RM², Ferrone S³, Ferris RL⁴.

¹Department of Immunology; University of Pittsburgh; Pittsburgh, PA USA.
²Department of Otolaryngology; University of Pittsburgh; Pittsburgh, PA USA.
³Department of Surgery; Massachusetts General Hospital; Harvard Medical School; Boston, MA USA.
⁴Department of Immunology; University of Pittsburgh; Pittsburgh, PA USA ; Department of Otolaryngology; University of Pittsburgh; Pittsburgh, PA USA ; Cancer Immunology Program; University of Pittsburgh Cancer Institute; Pittsburgh, PA USA.

 

Abstract

The epidermal growth factor receptor (EGFR) supports the escape of malignant cells from immunosurveillance by inhibiting the activation of signal transducer and activator of transcription 1 (STAT1) while promoting that of STAT3. We have recently demonstrated that protein tyrosine phosphatase, non-receptor type 11 (PTNP11, best known as SHP2), a phosphatase that operates downstream of EGFR, is responsible for the dephosphorylation of active STAT1 and for the inhibition of the antigen-processing machinery (APM), hence favoring tumor immunoescape. Thus, EGFR signaling may skew the tumor microenvironment to suppress cellular immune responses.

KEYWORDS:

APM; EGFR; SHP2; immunoescape; immunotherapy; pSTAT1; pSTAT3

Oncoimmunology. 2013 Dec 1;2(12):e27215. Epub 2013 Dec 5.

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913673/

Md. PhD. Fernando Concha. Ex-miembro del GII

Dieta y Depresión

Prospective study on long-term dietary patterns and incident depression in middle-aged and older women.

Chocano-Bedoya PO¹, O'Reilly EJ, Lucas M, Mirzaei F, Okereke OI, Fung TT, Hu FB, Ascherio A.

¹Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA. pchocano@hsph.harvard.edu

 

Abstract

BACKGROUND:

Although individual nutrients have been investigated in relation to depression risk, little is known about the overall role of diet in depression.

OBJECTIVE:

We examined whether long-term dietary patterns derived from a food-frequency questionnaire (FFQ) predict the development of depression in middle-aged and older women.

DESIGN:

We conducted a prospective study in 50,605 participants (age range: 50-77 y) without depression in the Nurses' Health Study at baseline (1996) who were followed until 2008. Long-term diet was assessed by using FFQs every 4 y since 1986. Prudent (high in vegetables) and Western (high in meats) patterns were identified by using a principal component analysis. We used 2 definitions for clinical depression as follows: a strict definition that required both a reported clinical diagnosis and use of antidepressants (3002 incident cases) and a broad definition that further included women who reported either a clinical diagnosis or antidepressant use (7413 incident cases).

RESULTS:

After adjustment for age, body mass index, and other potential confounders, no significant association was shown between the diet patterns and depression risk under the strict definition. Under the broad definition, women with the highest scores for the Western pattern had 15% higher risk of depression (95% CI: 1.04, 1.27; P-trend = 0.01) than did women with the lowest scores, but after additional adjustment for psychological scores at baseline, results were no longer significant (RR: 1.09; 95% CI: 0.99, 1.21; P-trend = 0.08).

CONCLUSION:

Overall, results of this large prospective study do not support a clear association between dietary patterns from factor analysis and depression risk.

Am J Clin Nutr. 2013 Sep;98(3):813-20. doi: 10.3945/ajcn.112.052761. Epub 2013 Jul 24.

http://ajcn.nutrition.org/content/98/3/813.long

Md. PhD. Patricia Chocano. Ex miembro del GII.

E. Coli Meningitis

E. coli Meningitis Presenting in a Patient with Disseminated Strongyloides stercoralis.

Gomez JB¹, Maque Y, Moquillaza MA, Anicama WE.

¹Department of Internal Medicine, Guillermo Almenara Irigoyen National Hospital, Lima, Peru.

 

Abstract

Introduction. Spontaneous Escherichia coli meningitis is an infrequent condition in adults and is associated with some predisposing factors, including severe Strongyloides stercoralis (SS) infections. Case Presentation. A 43-year-old Hispanic man, with history of travelling to the jungle regions of Peru and Brazil two decades ago, and who received prednisone due to Bell's palsy for three weeks before admission, presented to the Emergency Department with diarrhea, fever, and hematochezia. A week after admission he developed drowsiness, meningeal signs, abdominal distension, and constipation. A cerebrospinal fluid culture showed extended spectrum β -lactamase producing E. coli. A colonoscopy was performed and showed pancolitis. Three days after the procedure the patient became unstable and developed peritoneal signs. He underwent a laparotomy, which ended up in a total colectomy and partial proctectomy due to toxic megacolon. Three days later the patient died in the intensive care unit due to septic shock. Autopsy was performed and microscopic examination revealed the presence of multiple Strongyloides larvae throughout the body. Conclusion. Strongyloides stercoralis infection should be excluded in adults with spontaneous E. coli meningitis, especially, if gastrointestinal symptoms and history of travelling to an endemic area are present. Even with a proper diagnosis and management, disseminated strongyloidiasis has a poor prognosis. 

Case Rep Infect Dis. 2013;2013:424362. doi: 10.1155/2013/424362. Epub 2013 Nov 13.

http://www.hindawi.com/journals/criid/2013/424362/

Md. MSc. Yvan Maque. Ex-miembro del GII.

Chlamydia trachomatis e Inmunidad

Human female genital tract infection by the obligate intracellular bacterium Chlamydia trachomatis elicits robust Type 2 immunity.

Vicetti Miguel RD¹, Harvey SA, LaFramboise WA, Reighard SD, Matthews DB, Cherpes TL.

¹Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

 

Abstract

While Chlamydia trachomatis infections are frequently asymptomatic, mechanisms that regulate host response to this intracellular Gram-negative bacterium remain undefined. This investigation thus used peripheral blood mononuclear cells and endometrial tissue from women with or without Chlamydia genital tract infection to better define this response. Initial genome-wide microarray analysis revealed highly elevated expression of matrix metalloproteinase 10 and other molecules characteristic of Type 2 immunity (e.g., fibrosis and wound repair) in Chlamydia-infected tissue. This result was corroborated in flow cytometry and immunohistochemistry studies that showed extant upper genital tract Chlamydia infection was associated with increased co-expression of CD200 receptor and CD206 (markers of alternative macrophage activation) by endometrial macrophages as well as increased expression of GATA-3 (the transcription factor regulating TH2 differentiation) by endometrial CD4(+) T cells. Also among women with genital tract Chlamydia infection, peripheral CD3(+) CD4(+) and CD3(+) CD4(-) cells that proliferated in response to ex vivo stimulation with inactivated chlamydial antigen secreted significantly more interleukin (IL)-4 than tumor necrosis factor, interferon-γ, or IL-17; findings that repeated in T cells isolated from these same women 1 and 4 months after infection had been eradicated. Our results thus newly reveal that genital infection by an obligate intracellular bacterium induces polarization towards Type 2 immunity, including Chlamydia-specific TH2 development. Based on these findings, we now speculate that Type 2 immunity was selected by evolution as the host response to C. trachomatis in the human female genital tract to control infection and minimize immunopathological damage to vital reproductive structures.

PLoS One. 2013;8(3):e58565. doi: 10.1371/journal.pone.0058565. Epub 2013 Mar 13.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0058565

Md. Rodolfo Vicetti. Ex-miembro del GII.

Dermatología e Inmunología

Melanocitos en vitíligo y melanoma: una lección

entre autoinmunidad e inmunidad tumoral

  Julio E Valdivia-Silva1, Claudia Ramírez1

1Chemokines Biology Research Laboratory, Instituto de Investigaciones Biomédicas, UNAM, México D.F., México.

ABSTRACT 

Classically, vitiligo has been deined as a skin disease in which melanocytes (MC) are eradicated from lesional epidermis by MC-reactive T cells, as well as other non-immune and immune components, resulting in disiguring loss of pigment. Moreover, the absence or damage on MC has frequently been associated to a major risk to develop skin cancer including melanoma. However, patients with vitiligo have also shown 'non-pigmented' MC in epidermis similar to individuals with albinism, and these cells are apparently conferring resistance of developing melanoma. These seemingly contradictory facts are further complicated because, the MC antigens which are immunologically recognized are shared for both diseases producing fairly different results. An analysis of the similarities and differences between the autoimmunity observed in vitiligo and the tumour immunity observed in melanoma might lead to a better understanding of the MC' roles and the development of new therapies for both diseases. 

Dermatol PerU 2013; vol 23 (3)

http://sisbib.unmsm.edu.pe/bvrevistas/dermatologia/v23_n3/pdf/a03v23n3.pdf

Md PhD Julio Valdivia Silva. Fundador del GII

Inmunoterapia y Cáncer

Efficacy of DNA vaccines forming e7 recombinant retroviral virus-like particles for the treatment of human papillomavirus-induced cancers.

Lescaille G¹, Pitoiset F, Macedo R, Baillou C, Huret C, Klatzmann D, Tartour E, Lemoine FM, Bellier B.

¹Research Unit UMR CNRS 7211/INSERM 959, 75013 Paris, France.

 

Abstract

Human papillomavirus (HPV) is involved in the development of anogenital tumors and also in the development of oropharyngeal head and neck carcinomas, where HPV-16, expressing the E6 and E7 oncoproteins, is the most frequent serotype. Although vaccines encoding L1 and L2 capsid HPV proteins are efficient for the prevention of HPV infection, they are inadequate for treating established tumors. Hence, development of innovative vaccine therapies targeting E6/E7 is important for controlling HPV-induced cancers. We have engineered a nononcogenic mutated E7-specific plasmo-retroVLP vaccine (pVLP-E7), consisting of plasmid DNA, that is able to form recombinant retrovirus-based virus-like particles (VLPs) that display E7 antigen into murine leukemia virus Gag proteins pseudotyped with vesicular stomatitis virus envelope glycoprotein (VSV-G). pVLP-E7 vaccinations were studied for their ability to generate specific immune responses and for induction of protective immunity against tumor cell challenge in preventive and therapeutic models. The produced VLPs induce the maturation of human dendritic cells in vitro and mount specific E7 T cell responses. Intradermic vaccinations of mice with pVLP-E7 show their efficacy to generate antigen-specific T cell responses, to prevent and protect animals from early TC-1 tumor development compared with standard DNA or VLP immunizations. The vaccine efficacy was also evaluated for advanced tumors in mice vaccinated at various time after the injection of TC-1 cells. Data show that pVLP-E7 vaccination can cure mice with already established tumors only when combined with Toll-like receptor-7 (TLR7) and TLR9 agonists. Our findings provide evidence that pVLPs, combining the advantages of DNA and VLP vaccines, appear to be a promising strategy for the treatment of HPV-induced cancers.

Hum Gene Ther. 2013 May;24(5):533-44. doi: 10.1089/hum.2012.037. Epub 2013 May 6.

http://online.liebertpub.com/doi/abs/10.1089/hum.2012.037 

Md. PhD. Rodney Macedo. Past-president del GII.

Dieta y Sindrome Premenstrual

Intake of selected minerals and risk of premenstrual syndrome.

Chocano-Bedoya PO¹, Manson JE, Hankinson SE, Johnson SR, Chasan-Taber L, Ronnenberg AG, Bigelow C, Bertone-Johnson ER.

¹Department of Public Health, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003, USA.

 

Abstract

Iron, potassium, zinc, and other minerals might impact the development of premenstrual syndrome (PMS) through multiple mechanisms, but few studies have evaluated these relations. We conducted a case-control study nested within the prospective Nurses' Health Study II (1991-2001). Participants were free from PMS at baseline. After 10 years, 1,057 women were confirmed as PMS cases and 1,968 as controls. Mineral intake was assessed using food frequency questionnaires completed in 1991, 1995, and 1999. After adjustment for calcium intake and other factors, women in the highest quintile of nonheme iron intake had a relative risk of PMS of 0.64 (95% confidence interval (CI): 0.44, 0.92; P for trend = 0.04) compared with women in the lowest quintile. Women in the highest quintile of potassium intake had a relative risk of 1.46 (95% CI: 0.99, 2.15; P for trend = 0.04) compared with women in the lowest quintile. High intake of zinc from supplements was marginally associated with PMS (for intake of ≥25 mg/day vs. none, relative risk = 0.69, 95% CI: 0.46, 1.02; P for trend = 0.05). Intakes of sodium, magnesium, and manganese were unrelated to PMS risk. These findings suggest that dietary minerals may be useful in preventing PMS. Additional studies are needed to confirm these relations.

KEYWORDS:

dietary iron; minerals; premenstrual syndrome

Am J Epidemiol. 2013 May 15;177(10):1118-27. doi: 10.1093/aje/kws363. Epub 2013 Feb 26.

http://aje.oxfordjournals.org/content/177/10/1118.long

Md. PhD. Patricia Chocano. Ex miembro del GII.

Chlamydia trachomatis e Inmunidad

Transient detection of Chlamydial-specific Th1 memory cells in the peripheral circulation of women with history of Chlamydia trachomatis genital tract infection.

Vicetti Miguel RD¹, Reighard SD, Chavez JM, Rabe LK, Maryak SA, Wiesenfeld HC, Cherpes TL.

¹Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA.

 

Abstract

PROBLEM:

Development of safe and effective Chlamydia trachomatis vaccines requires better understanding of the host immune responses elicited by natural infection.

METHOD OF STUDY:

Peripheral blood mononuclear cells isolated from women with or without history of genital tract chlamydial infection were stimulated with inactivated C. trachomatis elementary bodies (EB) in ELISPOT assays that enumerated frequencies of cells producing interferon (IFN)-γ or interleukin (IL)-17.

RESULTS:

IFN-γ-positive cells were highest among women sampled 30-60 days after diagnosis of C. trachomatis infection and treatment initiation, while the numbers of IFN-γ-positive cells were equally low among uninfected women and women sampled <30 or >60 days after diagnosis of infection. Conversely, IL-17-positive cell numbers were uniformly low among all participants.

CONCLUSION:

Dramatically reduced numbers of Chlamydia-specific Th1 memory cells in the peripheral circulation of study participants sampled more than 2 months after diagnosis, and initiation of treatment provides new insight into the results from C. trachomatis vaccine trials, in which immunization with EB provided only short-lived protection. Our results also suggest that an effective vaccine against this weakly antigenic intracellular pathogen will need to generate immunological memory more durable than that elicited by natural infection.

© 2012 John Wiley & Sons A/S.

Am J Reprod Immunol. 2012 Dec;68(6):499-506. doi: 10.1111/aji.12008. Epub 2012 Aug 31.

http://onlinelibrary.wiley.com/doi/10.1111/aji.12008/abstract;jsessionid=B95D7E5E29926F60FB0D65C3E2DB60D8.f02t01

Md. Rodolfo Vicetti. Ex-miembro del GII. 

Chlamydia trachomatis e Inmunidad

Hypothesis: Chlamydia trachomatis infection of the female genital tract is controlled by Type 2 immunity.

Vicetti Miguel RD¹, Cherpes TL.

¹Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

 

Abstract

Chlamydia trachomatis is an obligate intracellular bacterium sexually transmitted to more than 90 million individuals each year. As this level of infectivity implies, C. trachomatis is a successful human parasite; a success facilitated by its ability to cause asymptomatic infection. Host defense against C. trachomatis in the female genital tract is not well defined, but current dogma suggests infection is controlled largely by T(H)1 immunity. Conversely, it is well established that T(H)2 immunity controls allergens, helminths, and other extracellular pathogens that cause repetitive or persistent T cell stimulation but do not induce the exuberant inflammation that drives T(H)1 and T(H)17 immunity. As C. trachomatis persists in female genital tract epithelial cells but does not elicit over tissue inflammation, we now posit that defense is maintained by Type 2 immune responses that control bacterial growth but minimize immunopathological damage to vital reproductive tract anatomy. Evaluation of this hypothesis may uncover novel mechanisms by which Type 2 immunity can control growth of C. trachomatis and other intracellular pathogens, while confirmation that T(H)2 immunity was selected by evolution to control C. trachomatis infection in the female genital tract will transform current research, now focused on developing vaccines that elicit strong, and therefore potentially tissue destructive, Chlamydia-specific T(H)1 immunity.

Copyright © 2012 Elsevier Ltd. All rights reserved.

Med Hypotheses. 2012 Dec;79(6):713-6. doi: 10.1016/j.mehy.2012.07.032. Epub 2012 Sep 15.

http://www.sciencedirect.com/science/article/pii/S0306987712003568

Md. Rodolfo Vicetti. Ex-miembro del GII.

Chlamydia trachomatis e Inmunidad

Brefeldin A, but not monensin, enables flow cytometric detection of interleukin-4 within peripheral T cells responding to ex vivo stimulation with Chlamydia trachomatis.

Vicetti Miguel RD¹, Maryak SA, Cherpes TL.

¹Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA. rdv4@pitt.edu

 

Abstract

Intracellular cytokine staining (ICS) assay optimization should include selection of suitable cytokine secretion inhibitors. Here, peripheral blood mononuclear cells (PBMC) from women with proven history of C. trachomatis genital tract infection were used to compare the ability of brefeldin A (BFA) and monensin (MN) to concurrently trap interferon-γ (IFN-γ), tumor necrosis factor (TNF), interleukin (IL)-4, and IL-17 within T cells responding to ex vivo stimulation with chlamydial antigen. While flow cytometric analyses showed similar intracellular levels of TNF, IFN-γ, and IL-17 among T cells treated with BFA or both BFA and MN, markedly more IL-4 was found inside T cells treated with BFA compared to those that received MN or BFA and MN. The latter findings oppose current ICS recommendations informing that ICS results are unaffected by concomitant use of BFA and MN, and also suggests that MN may be an unsuitable cytokine secretion inhibitor for ICS assays designed to measure intracellular IL-4 accumulation.

Copyright © 2012 Elsevier B.V. All rights reserved.

J Immunol Methods. 2012 Oct 31;384(1-2):191-5. doi: 10.1016/j.jim.2012.07.018. Epub 2012 Jul 29.

http://www.sciencedirect.com/science/article/pii/S0022175912002293

Md. Rodolfo Vicetti. Ex-miembro del GII.

Célula Dendríticas y Medroxyprogesterona

Dendritic cell activation and memory cell development are impaired among mice administered medroxyprogesterone acetate prior to mucosal herpes simplex virus type 1 infection.

Vicetti Miguel RD¹, Hendricks RL, Aguirre AJ, Melan MA, Harvey SA, Terry-Allison T, St Leger AJ, Thomson AW, Cherpes TL.

¹Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA.

 

Abstract

Epidemiological studies indicate that the exogenous sex steroid medroxyprogesterone acetate (MPA) can impair cell-mediated immunity, but mechanisms responsible for this observation are not well defined. In this study, MPA administered to mice 1 wk prior to HSV type 1 (HSV-1) infection of their corneal mucosa impaired initial expansion of viral-specific effector and memory precursor T cells and reduced the number of viral-specific memory T cells found in latently infected mice. MPA treatment also dampened expression of the costimulatory molecules CD40, CD70, and CD80 by dendritic cells (DC) in lymph nodes draining acute infection, whereas coculture of such DC with T cells from uninfected mice dramatically impaired ex vivo T cell proliferation compared with the use of DC from mice that did not receive MPA prior to HSV-1 infection. In addition, T cell expansion was comparable to that seen in untreated controls if MPA-treated mice were administered recombinant soluble CD154 (CD40L) concomitant with their mucosal infection. In contrast, the immunomodulatory effects of MPA were infection site dependent, because MPA-treated mice exhibited normal expansion of virus-specific T cells when infection was systemic rather than mucosal. Taken together, our results reveal that the administration of MPA prior to viral infection of mucosal tissue impairs DC activation, virus-specific T cell expansion, and development of virus-specific immunological memory.

J Immunol. 2012 Oct 1;189(7):3449-61. Epub 2012 Aug 31.

http://www.jimmunol.org/content/189/7/3449.long


Md. Rodolfo Vicetti. Ex-miembro del GII.

Dermatología e Inmunología

Mastocitos y basófilos y sus nuevas funciones en inmunología

 Julio E Valdivia-Silva 

1Chemokines Biology Research Laboratory, Instituto de Investigaciones Biomédicas, UNAM, México D.F., México.

ABSTRACT 

Mast cells and basophils have demonstrated to have both beneficial and detrimental functions for the immune system. Additionally to their classic role in pro-inflammatory responses to allergens, they are also involved directly in immunity against different pathogens. Because there are few animals models developed to investigate these cells in vivo, their functions during health and disease remain poorly understood. This review gives a short glance in the development and functional status of mast cells and basophils focusing on immunology concepts necessary to get a major understanding of the mechanisms of disease in different pathological states. 

DERMATOL PERU 2012; VOL 23

http://sisbib.unmsm.edu.pe/bvrevistas/dermatologia/v23_n2/pdf/a04v23n2.pdf

Md PhD Julio Valdivia Silva. Fundador del GII