The role of peroxisome proliferator-activated receptor ? 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 (PPAR?) in the modulation of host responses to EAEC in nourished and malnourished mice.

Methods/principal findings

Wild-type and T cell-specific PPAR? 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 PPAR? in T cells resulted in upregulation of TGF-?, 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 PPAR? 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 PPAR? as a novel therapeutic intervention for EAEC infection.

SUBMITTER: Philipson CW 

PROVIDER: S-EPMC3585146 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature