Lactobacillus rhamnosus GG Regulates Host IFN-I Through the RIG-I Signalling Pathway to Inhibit Herpes Simplex Virus Type 2 Infection

Probiotics Antimicrob Proteins. 2024 Dec;16(6):1966-1978. doi: 10.1007/s12602-023-10137-8. Epub 2023 Aug 25.

Abstract

Numerous recent studies have demonstrated that the commensal microbiota plays an important role in host immunity against infections. During the infection process, viruses can exhibit substantial and close interactions with the commensal microbiota. However, the associated mechanism remains largely unknown. Therefore, in this study, we explored the specific mechanisms by which the commensal microbiota modulates host immunity against viral infections. We found that the expression levels of type I interferon (IFN-I) and antiviral priming were significantly downregulated following the depletion of the commensal microbiota due to treatment with broad-spectrum antibiotics (ABX). In addition, we confirmed a unique molecular mechanism underlying the induction of IFN-I mediated by the commensal microbiota. In vivo and in vitro experiments confirmed that Lactobacillus rhamnosus GG (LGG) can suppress herpes simplex virus type 2 (HSV-2) infection by inducing IFN-I expression via the retinoic acid-inducible gene-I (RIG-I) signalling pathway. Therefore, the commensal microbiota-induced production of IFN-I provides a potential therapeutic approach to combat viral infections. Altogether, understanding the complexity and the molecular aspects linking the commensal microbiota to health will help provide the basis for novel therapies already being developed.

Keywords: Lactobacillus rhamnosus GG; Commensal microbiota; Herpes simplex virus type 2; Interferon type I; RIG-I.

MeSH terms

  • Animals
  • DEAD Box Protein 58 / genetics
  • DEAD Box Protein 58 / metabolism
  • Female
  • Herpes Simplex / immunology
  • Herpesvirus 2, Human* / immunology
  • Herpesvirus 2, Human* / physiology
  • Humans
  • Interferon Type I* / immunology
  • Interferon Type I* / metabolism
  • Lacticaseibacillus rhamnosus* / physiology
  • Mice
  • Mice, Inbred C57BL
  • Probiotics / pharmacology
  • Signal Transduction*

Substances

  • Interferon Type I
  • DEAD Box Protein 58