STING-Dependent Type I IFN Production Inhibits Cell-Mediated Immunity to Listeria monocytogenes

PLoS Pathogens

Kristina A. Archer¹  Daniel A. Portnoy¹  Juliana Durack¹ 

[1] Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, United States of America

关键词: Listeria monocytogenes;    Cytotoxic T cells;    T cells;    Cell-mediated immunity;    Immunity;    Immune response;    Spleen;    Cytokines;   

DOI  :  10.1371/journal.ppat.1003861

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Infection with Listeria monocytogenes strains that enter the host cell cytosol leads to a robust cytotoxic T cell response resulting in long-lived cell-mediated immunity (CMI). Upon entry into the cytosol, L. monocytogenes secretes cyclic diadenosine monophosphate (c-di-AMP) which activates the innate immune sensor STING leading to the expression of IFN-β and co-regulated genes. In this study, we examined the role of STING in the development of protective CMI to L. monocytogenes. Mice deficient for STING or its downstream effector IRF3 restricted a secondary lethal challenge with L. monocytogenes and exhibited enhanced immunity that was MyD88-independent. Conversely, enhancing STING activation during immunization by co-administration of c-di-AMP or by infection with a L. monocytogenes mutant that secretes elevated levels of c-di-AMP resulted in decreased protective immunity that was largely dependent on the type I interferon receptor. These data suggest that L. monocytogenes activation of STING downregulates CMI by induction of type I interferon.

【 授权许可】

CC BY