IL-13 Attenuates Gastrointestinal Candidiasis in Normal and Immunodeficient RAG-2−/− Mice via Peroxisome Proliferator-Activated Receptor-γ Activation

Abstract We recently demonstrated that in vitro peroxisome proliferator-activated receptor-γ (PPARγ) activation of mouse peritoneal macrophages by IL-13 or PPARγ ligands promotes uptake and killing of Candida albicans through mannose receptor overexpression. In this study, we demonstrate that i.p. treatment of immunocompetent and immunodeficient (RAG-2−/−) mice with natural and synthetic PPARγ-specific ligands or with IL-13 decreases C. albicans colonization of the gastrointestinal (GI) tract 8 days following oral infection with the yeast. We also showed that Candida GI infection triggers macrophage recruitment in cecum mucosa. These mucosal macrophages, as well as peritoneal macrophages, overexpress the mannose receptor after IL-13 and rosiglitazone treatments. The treatments promote macrophage activation against C. albicans as suggested by the increased ability of peritoneal macrophages to phagocyte C. albicans and to produce reactive oxygen intermediates after yeast challenge. These effects on C. albicans GI infection and on macrophage activation are suppressed by treatment of mice with GW9662, a selective PPARγ antagonist, and are reduced in PPARγ+/− mice. Overall, these data demonstrate that IL-13 or PPARγ ligands attenuate C. albicans infection of the GI tract through PPARγ activation and hence suggest that PPARγ ligands may be of therapeutic value in esophageal and GI candidiasis in immunocompromised patients.