IRF5 deficiency severely impairs the development of T helper 1 responses following Leishmania donovani infection. (37.3)

Abstract

Abstract The transcription factor Interferon Regulatory Factor 5 (IRF5) has been shown to be involved in the induction of proinflammatory cytokines in response to viral infections and TLR activation and to play an essential role in the innate inflammatory response. In this study, the experimental model of visceral leishmaniasis was used to investigate the role of IRF5 in the generation of Th1 responses and subsequent formation of Th1-type liver granulomas in Leishmania donovani infected mice. Here we show that IRF5 deficiency severely impairs the development of Th1 responses to L.donovani leading to the formation of Th2-type-like granulomas. These granulomas are characterized by a strong IL-4 response, upregulation of arginase 1 and Fizz1 mRNA and concomitant low iNOS expression. This study identifies IRF5 as a critical molecular switch for the development of Th1 immune responses following L.donovani infections and as an important molecule in the regulation of arginase 1 and iNOS expression.