The microbiota plays a critical role in the reactivity of lung immune components to innate ligands.
Animals
Bronchoalveolar Lavage Fluid
/ chemistry
Cytokines
/ genetics
Gastrointestinal Microbiome
/ physiology
Gene Expression Regulation
/ drug effects
Germ-Free Life
Inflammation
/ chemically induced
Lipopolysaccharides
/ toxicity
Lung
/ immunology
Lung Diseases
/ chemically induced
Male
Mice
Specific Pathogen-Free Organisms
Tissue Culture Techniques
Toll-Like Receptor 4
/ genetics
alveolar macrophages
germ-free
innate immune memory
lung explants
microbiota
respiratory syncytial virus
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
revised:
18
12
2020
received:
21
10
2020
accepted:
22
12
2020
entrez:
14
3
2021
pubmed:
15
3
2021
medline:
22
7
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33715218
doi: 10.1096/fj.202002338R
doi:
Substances chimiques
Cytokines
0
Lipopolysaccharides
0
TLR4 protein, human
0
Toll-Like Receptor 4
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e21348Informations de copyright
© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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