1. Secretion of c-di-AMP by Listeria monocytogenes Leads to a STING-Dependent Antibacterial Response during Enterocolitis
- Author
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Louie, Alexander, Bhandula, Varaang, and Portnoy, Daniel A
- Subjects
Microbiology ,Biological Sciences ,Biomedical and Clinical Sciences ,Biodefense ,Infectious Diseases ,Genetics ,Emerging Infectious Diseases ,Foodborne Illness ,Digestive Diseases ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Animals ,Dinucleoside Phosphates ,Enterocolitis ,Flow Cytometry ,Immunity ,Innate ,Interferon Type I ,Listeria monocytogenes ,Listeriosis ,Membrane Proteins ,Mice ,Mice ,Inbred C57BL ,Mice ,Knockout ,Monocytes ,Signal Transduction ,gastrointestinal infection ,innate immunity ,monocytes ,pathogenesis ,Agricultural and Veterinary Sciences ,Medical and Health Sciences ,Immunology ,Medical microbiology - 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. Listeria monocytogenes is a foodborne, facultative intracellular pathogen that secretes c-di-AMP and activates STING, yet the in vivo 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 L. monocytogenes-induced enterocolitis. Infection with a L. monocytogenes 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 L. monocytogenes-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.
- Published
- 2020