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: Kristina A Archer, Juliana Durack, Daniel A Portnoy
• Journal: PLoS pathogens (PLoS Pathog) Vol. 10 Issue 1 Pg. e1003861 (Jan 2014) ISSN: 1553-7374 [Electronic] United States
• PMID: 24391507 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Dinucleoside Phosphates
• Membrane Proteins
• Sting1 protein, mouse
• cyclic diadenosine phosphate
• Interferon-beta

Topics

• Animals
• CD8-Positive T-Lymphocytes (immunology, pathology)
• Dinucleoside Phosphates (immunology)
• Gene Expression Regulation (genetics, immunology)
• Immunity, Cellular
• Interferon-beta (immunology)
• Listeria monocytogenes (immunology)
• Listeriosis (genetics, immunology, pathology)
• Membrane Proteins (genetics, immunology)
• Mice
• Mice, Knockout