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

KA Archer, J Durack, DA Portnoy - PLoS pathogens, 2014 - journals.plos.org
KA Archer, J Durack, DA Portnoy
PLoS pathogens, 2014journals.plos.org
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 …
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.
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