Critical Role of IRF-5 in the Development of T helper 1 responses to Leishmania donovani infection

PLoS Pathogens

Simona Stäger¹  Trupti Joshi²  Rashmi Bankoti²  Paula M. Pitha³  Andrea Paun³ 

[1] Biology Department, The Johns Hopkins University, Baltimore, Maryland, United States of America;Department of Molecular and Comparative Pathobiology, The Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America;Sidney Kimmel Comprehensive Center, The Johns Hopkins University, Baltimore, Maryland, United States of America

关键词: Leishmania donovani;    T cells;    Parasitic diseases;    Spleen;    Macrophages;    Immune response;    Leishmania;    Cytokines;   

DOI  :  10.1371/journal.ppat.1001246

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The transcription factor Interferon Regulatory Factor 5 (IRF-5) 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, we used the experimental model of visceral leishmaniasis to investigate the role of IRF-5 in the generation of Th1 responses and in the formation of Th1-type liver granulomas in Leishmania donovani infected mice. We show that TLR7-mediated activation of IRF-5 is essential for the development of Th1 responses to L. donovani in the spleen during chronic infection. We also demonstrate that IRF-5 deficiency leads to the incapacity to control L. donovani infection in the liver and to the formation of smaller granulomas. Granulomas in Irf5-/- mice are characterized by an increased IL-4 and IL-10 response and concomitant low iNOS expression. Collectively, these results identify IRF-5 as a critical molecular switch for the development of Th1 immune responses following L. donovani infections and reveal an indirect role of IRF-5 in the regulation of iNOS expression.

【 授权许可】

CC BY