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Host Response and Inflammation | Spotlight

Secretion of c-di-AMP by Listeria monocytogenes Leads to a STING-Dependent Antibacterial Response during Enterocolitis

Alexander Louie, Varaang Bhandula, Daniel A. Portnoy
Nancy E. Freitag, Editor
Alexander Louie
aDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA
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Varaang Bhandula
aDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA
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Daniel A. Portnoy
aDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA
bDepartment of Plant and Microbial Biology, University of California, Berkeley, Berkeley, California, USA
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Nancy E. Freitag
University of Illinois at Chicago
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DOI: 10.1128/IAI.00407-20
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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.

FOOTNOTES

    • Received 3 July 2020.
    • Returned for modification 10 August 2020.
    • Accepted 27 September 2020.
    • Accepted manuscript posted online 5 October 2020.
  • Supplemental material is available online only.

  • Copyright © 2020 American Society for Microbiology.

All Rights Reserved.

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Secretion of c-di-AMP by Listeria monocytogenes Leads to a STING-Dependent Antibacterial Response during Enterocolitis
Alexander Louie, Varaang Bhandula, Daniel A. Portnoy
Infection and Immunity Nov 2020, 88 (12) e00407-20; DOI: 10.1128/IAI.00407-20

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Secretion of c-di-AMP by Listeria monocytogenes Leads to a STING-Dependent Antibacterial Response during Enterocolitis
Alexander Louie, Varaang Bhandula, Daniel A. Portnoy
Infection and Immunity Nov 2020, 88 (12) e00407-20; DOI: 10.1128/IAI.00407-20
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KEYWORDS

Listeria monocytogenes
gastrointestinal infection
innate immunity
monocytes
pathogenesis

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