STING-Dependent Type I IFN Production Inhibits Cell-Mediated Immunity to Listeria monocytogenes
|
| |
| Authors: | Kristina A. Archer Juliana Durack Daniel A. Portnoy |
| |
| Affiliation: | 1. Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, United States of America.; 2. School of Public Health, University of California, Berkeley, Berkeley, California, United States of America.; University of Toronto, Canada, |
| |
| Abstract: | 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. |
| |
| Keywords: | |
|
|
