STING Promotes Intestinal IgA Production by Regulating Acetate-producing Bacteria to Maintain Host-microbiota Mutualism

Tianming Yu, Wenjing Yang, Suxia Yao, Yanbo Yu, Maki Wakamiya, George Golovko, Yingzi Cong

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Background: Intestinal Immunoglobulin A (IgA) is crucial in maintaining host-microbiota mutualism and gut homeostasis. It has been shown that many species of gut bacteria produce cyclic dinucleotides, along with an abundance of microbiota-derived DNA present within the intestinal lumen, which triggers the tonic activation of the cytosolic cGAS-STING pathway. However, the role of STING in intestinal IgA remains poorly understood. We further investigated whether and how STING affects intestinal IgA response. Methods: Intestinal IgA was determined between wild-type (WT) mice and Sting-/- mice in steady conditions and upon enteric Citrobacter rodentium infection. STING agonists were used to stimulating B cells or dendritic cells in vitro. Gut microbiota composition was examined by 16S ribosomal RNA gene sequencing. Bacteria metabolomics functional analyses was performed by PICRUSt2. Fecal short-chain fatty acid (SCFA) was determined by Mass spectrometry and Cedex Bio Analyzer. Gut bacteria from WT mice and Sting-/- mice were transferred into germ-free mice and antibiotic-pretreated mice. Results: Intestinal IgA response was impaired in Sting-/- mice. However, STING agonists did not directly stimulate B cells or dendritic cells to induce IgA. Interestingly, Sting-/- mice displayed altered gut microbiota composition with decreased SCFA-producing bacteria and downregulated SCFA fermentation pathways. Transfer of fecal bacteria from Sting-/- mice induced less IgA than that from WT mice in germ-free mice and antibiotic-pretreated mice, which is mediated by GPR43. Acetate, the dominant SCFA, was decreased in Sting-/- mice, and supplementation of acetate restored intestinal IgA production in Sting-/- mice. Conclusions: STING promotes intestinal IgA by regulating acetate-producing gut bacteria.

Original languageEnglish (US)
Pages (from-to)946-959
Number of pages14
JournalInflammatory bowel diseases
Volume29
Issue number6
DOIs
StatePublished - Jun 1 2023

Keywords

  • fermentation
  • gut IgA
  • microbiota

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

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