Epstein Barr Virus-Induced 3 (EBI3) Together with IL-12 Negatively Regulates T Helper 17-Mediated Immunity to Listeria monocytogenes Infection

PLoS Pathogens

Tomohide Yamazaki¹  Hoyong Lim²  Gustavo J. Martinez²  Seon Hee Chang²  Chen Dong²  Joseph M. Reynolds²  Yeonseok Chung²  Yongliang Zhang²  Byung-Seok Kim³  Mark Birkenbach³ 

[1] Center for Immunology and Autoimmune Diseases, Institute of Molecular Medicine, The University of Texas Medical School at Houston, Houston, Texas, United States of America;Department of Immunology and Center for Inflammation and Cancer, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America;The Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, Texas, United States of America

关键词: T cells;    Mouse models;    Intracellular pathogens;    Cytokines;    Cytotoxic T cells;    Listeria monocytogenes;    Spleen;    Pathogens;   

DOI  :  10.1371/journal.ppat.1003628

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Although the protective functions by T helper 17 (Th17) cytokines against extracellular bacterial and fungal infection have been well documented, their importance against intracellular bacterial infection remains unclear. Here, we investigated the contribution of Th17 responses to host defense against intracellular bacteria Listeria monocytogenes and found that Th17 cell generation was suppressed in this model. Unexpectedly, mice lacking both p35 and EBI3 cleared L. monocytogenes as efficiently as wild-type mice, whereas p35-deficient mice failed to do so. Furthermore, both innate cells and pathogen-specific T cells from double-deficient mice produced significantly higher IL-17 and IL-22 compared to wild-type mice. The bacterial burden in the liver of double-deficient mice treated with anti-IL-17 was significantly increased compared to those receiving a control Ab. Transfer of Th17 cells specific for listeriolysin O as well as administration of IL-17 and IL-22 significantly suppressed bacterial growth in p35-deficient mice, indicating the critical contribution of Th17 responses to host defense against the intracellular pathogen in the absence of IL-12 and proper Th1 responses. Our findings unveil a novel immune evasion mechanism whereby the intracellular bacteria exploit IL-27EBI3 to suppress Th17-mediated protective immunity.

【 授权许可】

CC BY