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dc.contributorVirginia Techen_US
dc.contributor.authorPhilipson, Casandra W.en_US
dc.contributor.authorBassaganya-Riera, Josepen_US
dc.contributor.authorViladomiu, Monicaen_US
dc.contributor.authorPedragosa, Mireiaen_US
dc.contributor.authorGuerrant, Richard L.en_US
dc.contributor.authorRoche, James K.en_US
dc.contributor.authorHontecillas, Raquelen_US
dc.date.accessioned2014-06-17T20:12:09Z
dc.date.available2014-06-17T20:12:09Z
dc.date.issued2013-02-28en_US
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_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://hdl.handle.net/10919/49002
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_US
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_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.subjectBacterial pathogensen_US
dc.subjectColonen_US
dc.subjectCytokinesen_US
dc.subjectGene expressionen_US
dc.subjectImmune responseen_US
dc.subjectInflammationen_US
dc.subjectNeutrophisen_US
dc.subjectT cellsen_US
dc.titleThe Role of Peroxisome Proliferator-Activated Receptor γ in Immune Responses to Enteroaggregative Escherichia coli Infectionen_US
dc.typeArticleen_US
dc.identifier.urlhttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0057812en_US
dc.date.accessed2014-05-06en_US
dc.title.serialPLoS ONEen_US
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0057812


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