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

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. © 2014 archer et al.