MAVS deficiency induces gut dysbiotic microbiota conferring a proallergic phenotype

Proc Natl Acad Sci U S A. 2018 Oct 9;115(41):10404-10409. doi: 10.1073/pnas.1722372115. Epub 2018 Sep 24.

Abstract

Prominent changes in the gut microbiota (referred to as "dysbiosis") play a key role in the development of allergic disorders, but the underlying mechanisms remain unknown. Study of the delayed-type hypersensitivity (DTH) response in mice contributed to our knowledge of the pathophysiology of human allergic contact dermatitis. Here we report a negative regulatory role of the RIG-I-like receptor adaptor mitochondrial antiviral signaling (MAVS) on DTH by modulating gut bacterial ecology. Cohousing and fecal transplantation experiments revealed that the dysbiotic microbiota of Mavs-/- mice conferred a proallergic phenotype that is communicable to wild-type mice. DTH sensitization coincided with increased intestinal permeability and bacterial translocation within lymphoid organs that enhanced DTH severity. Collectively, we unveiled an unexpected impact of RIG-I-like signaling on the gut microbiota with consequences on allergic skin disease outcome. Primarily, these data indicate that manipulating the gut microbiota may help in the development of therapeutic strategies for the treatment of human allergic skin pathologies.

Keywords: MAVS; RIG-like receptors; allergic skin pathologies; dysbiosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / physiology*
  • Animals
  • Disease Models, Animal
  • Dysbiosis / complications*
  • Female
  • Gastrointestinal Microbiome / immunology*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Hypersensitivity / etiology*
  • Hypersensitivity / metabolism
  • Hypersensitivity / pathology
  • Intestines / immunology*
  • Intestines / microbiology
  • Intestines / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phenotype
  • Signal Transduction
  • Skin Diseases, Bacterial / etiology*
  • Skin Diseases, Bacterial / metabolism
  • Skin Diseases, Bacterial / pathology

Substances

  • Adaptor Proteins, Signal Transducing
  • Homeodomain Proteins
  • IPS-1 protein, mouse
  • RAG-1 protein