Secretion of C-di-AMP by Listeria Monocytogenes Leads to a STING-Dependent Antibacterial Response During Enterocolitis

Overview

Journal Infect Immun

Publisher American Society for Microbiology

Specialty Allergy & Immunology

Date 2020 Oct 6

PMID 33020211

Citations 9

Authors

Alexander Louie

Varaang Bhandula

Daniel A Portnoy

Affiliations

Soon will be listed here.

Abstract

Stimulator of interferon genes (STING) acts as a cytoplasmic signaling hub of innate immunity that is activated by host-derived or bacterially derived cyclic dinucleotides. is a foodborne, facultative intracellular pathogen that secretes c-di-AMP and activates STING, yet the role of the STING pathway during bacterial pathogenesis remains unclear. In this study, we found that STING-deficient mice had increased weight loss and roughly 10-fold-increased systemic bacterial burden during -induced enterocolitis. Infection with a mutant impaired in c-di-AMP secretion failed to elicit a protective response, whereas a mutant with increased c-di-AMP secretion triggered enhanced protection. Type I interferon (IFN) is a major output of STING signaling; however, disrupting IFN signaling during -induced enterocolitis did not recapitulate STING deficiency. In the absence of STING, the intestinal immune response was associated with a reduced influx of inflammatory monocytes. These studies suggest that in barrier sites such as the intestinal tract, where pathogen-associated molecular patterns are abundant, cytosolic surveillance systems such as STING are well positioned to detect pathogenic bacteria.

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