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Microbiota-derived acetate protects against respiratory syncytial virus infection through a GPR43-type 1 interferon

Krist Helen Antunes1, José Luís Fachi2, Rosemeire de Paula2

  • 1Laboratory of Clinical and Experimental Immunology, Infant Center, School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, 90610-000, RS, Brazil.

Nature Communications
|July 24, 2019
PubMed

Insights

A high-fiber diet protects infant mice from severe respiratory syncytial virus (RSV) infection by promoting acetate production. Acetate enhances the interferon-beta (IFN-β) response, reducing viral load and lung inflammation.

Area of Science:

  • Microbiology
  • Immunology
  • Virology

Background:

  • Severe respiratory syncytial virus (RSV) infection poses a significant health risk, causing substantial morbidity and mortality in infants under two years old.
  • The gut microbiome plays a crucial role in host immunity and response to infections.

Purpose of the Study:

  • To investigate the protective effects of a high-fiber diet against RSV infection in a mouse model.
  • To elucidate the mechanisms underlying dietary protection, focusing on the role of intestinal microbiota and acetate.

Main Methods:

  • Mice were fed a high-fiber diet and subsequently infected with RSV.
  • Acetate levels, interferon-beta (IFN-β) response, and expression of interferon-stimulated genes were measured.
  • Experiments were conducted using wild-type and Gpr43-deficient (Gpr43-/-) mice, as well as pulmonary epithelial cell lines.
  • The role of Type 1 IFN signaling via the IFN-1 receptor (IFNAR) was assessed.

Main Results:

  • A high-fiber diet conferred protection against RSV infection in mice, dependent on intestinal microbiota and acetate production.
  • Oral acetate administration enhanced the IFN-β response by upregulating interferon-stimulated genes in the lungs, leading to reduced viral load and pulmonary inflammation.
  • Type 1 IFN signaling through IFNAR was critical for acetate's antiviral activity in both cell lines and infected mice.
  • Activation of Gpr43 in lung epithelial cells was essential for acetate's protective effects, as these were abolished in Gpr43-/- mice.

Conclusions:

  • Acetate, produced from dietary fiber by gut microbiota, exhibits significant antiviral effects against RSV infection.
  • The protective mechanism involves the induction of IFN-β response in lung epithelial cells via Gpr43 activation and Type 1 IFN signaling through IFNAR.
  • These findings highlight a novel dietary intervention strategy for managing RSV infections.

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