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The microbiota plays a critical role in the reactivity of lung immune components to innate ligands
Author(s) -
Marquant Quentin,
Laubreton Daphné,
Drajac Carole,
Mathieu Elliot,
Bouguyon Edwige,
Noordine MarieLouise,
Remot Aude,
Riffault Sabine,
Thomas Muriel,
Descamps Delphyne
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202002338r
Subject(s) - innate immune system , immune system , immunology , inflammation , tlr4 , biology , lipopolysaccharide , gut flora , immunity , innate lymphoid cell , lung , toll like receptor , pattern recognition receptor , microbiome , pathogen associated molecular pattern , microbiology and biotechnology , medicine , bioinformatics
The gut microbiota contributes to shaping efficient and safe immune defenses in the gut. However, little is known about the role of the gut and/or lung microbiota in the education of pulmonary innate immune responses. Here, we tested whether the endogenous microbiota in general can modulate the reactivity of pulmonary tissue to pathogen stimuli by comparing the response of specific‐pathogen‐free (SPF) and germ‐free (GF) mice. Thus, we observed earlier and greater inflammation in the pulmonary compartment of GF mice than that of SPF mice after intranasal instillation to lipopolysaccharide (LPS), a component of Gram‐negative bacteria. Toll‐like receptor 4 (TLR4) was more abundantly expressed in the lungs of GF mice than those of SPF mice at steady state, which could predispose the innate immunity of GF mice to strongly react to the environmental stimuli. Lung explants were stimulated with different TLR agonists or infected with the human airways pathogen, respiratory syncytial virus (RSV), resulting in greater inflammation under almost all conditions for the GF explants. Finally, alveolar macrophages (AM) from GF mice presented a higher innate immune response upon RSV infection than those of SPF mice. Overall, these data suggest that the presence of microbiota in SPF mice induced a process of innate immune tolerance in the lungs by a mechanism which remains to be elucidated. Our study represents a step forward to establishing the link between the microbiota and the immune reactivity of the lungs.