The Role of Peroxisome Proliferator-Activated Receptor γ in Immune Responses to Enteroaggregative Escherichia coli Infection

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dc.contributorVirginia Techen
dc.contributor.authorPhilipson, Casandra W.en
dc.contributor.authorBassaganya-Riera, Josepen
dc.contributor.authorViladomiu, Monicaen
dc.contributor.authorPedragosa, Mireiaen
dc.contributor.authorGuerrant, Richard L.en
dc.contributor.authorRoche, James K.en
dc.contributor.authorHontecillas, Raquelen
dc.date.accessed2014-05-06en
dc.date.accessioned2014-06-17T20:12:09Zen
dc.date.available2014-06-17T20:12:09Zen
dc.date.issued2013-02-28en
dc.description.abstractBackground: Enteroaggregative Escherichia coli (EAEC) is recognized as an emerging cause of persistent diarrhea and enteric disease worldwide. Mucosal immunity towards EAEC infections is incompletely understood due in part to the lack of appropriate animal models. This study presents a new mouse model and investigates the role of peroxisome proliferator-activated receptor gamma (PPARγ) in the modulation of host responses to EAEC in nourished and malnourished mice. Methods/Principal Findings: Wild-type and T cell-specific PPARγ null C57BL/6 mice were fed protein-deficient diets at weaning and challenged with 5×109cfu EAEC strain JM221 to measure colonic gene expression and immune responses to EAEC. Antigen-specific responses to E. coli antigens were measured in nourished and malnourished mice following infection and demonstrated the immunosuppressive effects of malnutrition at the cellular level. At the molecular level, both pharmacological blockade and deletion of PPARγ in T cells resulted in upregulation of TGF-β, IL-6, IL-17 and anti-microbial peptides, enhanced Th17 responses, fewer colonic lesions, faster clearance of EAEC, and improved recovery. The beneficial effects of PPARγ blockade on weight loss and EAEC clearance were abrogated by neutralizing IL-17 in vivo. Conclusions: Our studies provide in vivo evidence supporting the beneficial role of mucosal innate and effector T cell responses on EAEC burden and suggest pharmacological blockade of PPARγ as a novel therapeutic intervention for EAEC infection.en
dc.description.sponsorshipThis work was supported in part by National Institutes of Health 5R01AT004308 to JB-R, National Institute of Allergy and Infectious Diseases Contract No. HHSN272201000056C to JB-R and funds from the Nutritional Immunology and Molecular Medicine Laboratory. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.identifier.citationPhilipson CW, Bassaganya-Riera J, Viladomiu M, Pedragosa M, Guerrant RL, et al. (2013) The Role of Peroxisome Proliferator-Activated Receptor γ in Immune Responses to Enteroaggregative Escherichia coli Infection. PLoS ONE 8(2): e5781en
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0057812en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://hdl.handle.net/10919/49002en
dc.identifier.urlhttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0057812en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectBacterial pathogensen
dc.subjectColonen
dc.subjectCytokinesen
dc.subjectGene expressionen
dc.subjectImmune responseen
dc.subjectInflammationen
dc.subjectNeutrophisen
dc.subjectT cellsen
dc.titleThe Role of Peroxisome Proliferator-Activated Receptor γ in Immune Responses to Enteroaggregative Escherichia coli Infectionen
dc.title.serialPLoS ONEen
dc.typeArticle - Refereeden

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