title: STING-dependent type I IFN production inhibits cell-mediated immunity to Listeria monocytogenes.
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.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, United States of America.
authors.forename: Kristina A
authors.initials: KA
authors.lastname: Archer
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, United States of America.
authors.forename: Juliana
authors.initials: J
authors.lastname: Durack
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, United States of America ; School of Public Health, University of California, Berkeley, Berkeley, California, United States of America.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Portnoy
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D015226:Dinucleoside Phosphates / Q000276:immunology; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular; D016899:Interferon-beta / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D000099197:STING Protein
chemical_list: D015226:Dinucleoside Phosphates; D016899:Interferon-beta; D008565:Membrane Proteins; C530855:Sting1 protein, mouse; D000099197:STING Protein; C528998:cyclic diadenosine phosphate