Type I Interferons Induce T Regulatory 1 Responses and Restrict Humoral Immunity during Experimental Malaria

PLoS Pathogens

Noah S. Butler¹  Bradly E. Burke²  Amy C. Graham²  Rosemary L. Pope²  Ryan A. Zander²  Jenna J. Guthmiller²  Daniel J.J. Carr² 

[1] Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America;Departments of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America

关键词: T helper cells;    Parasitic diseases;    Plasmodium;    Humoral immunity;    Malaria;    Malarial parasites;    Cloning;    Antibodies;   

DOI  :  10.1371/journal.ppat.1005945

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

CD4 T cell-dependent antibody responses are essential for limiting Plasmodium parasite replication and the severity of malaria; however, the factors that regulate humoral immunity during highly inflammatory, Th1-biased systemic infections are poorly understood. Using genetic and biochemical approaches, we show that Plasmodium infection-induced type I interferons limit T follicular helper accumulation and constrain anti-malarial humoral immunity. Mechanistically we show that CD4 T cell-intrinsic type I interferon signaling induces T-bet and Blimp-1 expression, thereby promoting T regulatory 1 responses. We further show that the secreted effector cytokines of T regulatory 1 cells, IL-10 and IFN-γ, collaborate to restrict T follicular helper accumulation, limit parasite-specific antibody responses, and diminish parasite control. This circuit of interferon-mediated Blimp-1 induction is also operational during chronic virus infection and can occur independently of IL-2 signaling. Thus, type I interferon-mediated induction of Blimp-1 and subsequent expansion of T regulatory 1 cells represent generalizable features of systemic, inflammatory Th1-biased viral and parasitic infections that are associated with suppression of humoral immunity.

【 授权许可】

CC BY