STING-Dependent Type I IFN Production Inhibits Cell-Mediated Immunity to <i>Listeria monocytogenes</i>

<div><p>Infection with <i>Listeria monocytogenes</i> 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, <i>L. monocytogenes</i> 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 <i>L. monocytogenes</i>. Mice deficient for STING or its downstream effector IRF3 restricted a secondary lethal challenge with <i>L. monocytogenes</i> 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 <i>L. monocytogenes</i> 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 <i>L. monocytogenes</i> activation of STING downregulates CMI by induction of type I interferon.</p></div