title: The role of peroxisome proliferator-activated receptor γ in immune responses to enteroaggregative Escherichia coli infection.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  Wild-type and T cell-specific PPARγ null C57BL/6 mice were fed protein-deficient diets at weaning and challenged with 5×10(9)cfu 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.
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, Virginia, United States of America.
authors.forename: Casandra W
authors.initials: CW
authors.lastname: Philipson
authors.forename: Josep
authors.initials: J
authors.lastname: Bassaganya-Riera
authors.forename: Monica
authors.initials: M
authors.lastname: Viladomiu
authors.forename: Mireia
authors.initials: M
authors.lastname: Pedragosa
authors.forename: Richard L
authors.initials: RL
authors.lastname: Guerrant
authors.forename: James K
authors.initials: JK
authors.lastname: Roche
authors.forename: Raquel
authors.initials: R
authors.lastname: Hontecillas
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D058491:Bacterial Load / Q000235:genetics / Q000276:immunology; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D004926:Escherichia coli / Q000276:immunology / Q000502:physiology*; D004927:Escherichia coli Infections / Q000150:complications / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D055786:Gene Knockout Techniques; D020381:Interleukin-17 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D044342:Malnutrition / Q000150:complications; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D013997:Time Factors
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D000942:Antigens, Bacterial; D020381:Interleukin-17; D047495:PPAR gamma