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The microbiota plays a critical role in the reactivity of lung immune components to innate ligands

Title: The microbiota plays a critical role in the reactivity of lung immune components to innate ligands
Authors: Marquant, Quentin; Laubreton, Daphné; Drajac, Carole; Mathieu, Elliot; Bouguyon, Edwige; Noordine, Marie‐louise; Remot, Aude; Riffault, Sabine; Thomas, Muriel; Descamps, Delphyne
Contributors: Virologie et Immunologie Moléculaires (VIM (UR 0892)); Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); MICrobiologie de l'ALImentation au Service de la Santé (MICALIS); AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Infectiologie et Santé Publique (ISP); Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); INRAE; Région Ile‐de‐France (Domaine d'Intérêt Majeur : DIM-Malinf and DIM-OneHealth); Fondation Air Liquide; ANR-13-BSV3-0016,SyncBreg,Signature moléculaire et fonction des lymphocytes B régulateurs dans l'infection VRS(2013)
Source: ISSN: 0892-6638.
Publisher Information: CCSD; Federation of American Society of Experimental Biology
Publication Year: 2021
Collection: Université François-Rabelais de Tours: HAL
Subject Terms: alveolar macrophages; germ-free; innate immune memory; lung explants; microbiota; respiratory syncytial virus; [SDV]Life Sciences [q-bio]
Description: International audience ; 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.
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/33715218; PUBMED: 33715218; WOS: 000635216100014
DOI: 10.1096/fj.202002338R
Availability: https://hal.inrae.fr/hal-03169721; https://doi.org/10.1096/fj.202002338R
Rights: http://creativecommons.org/licenses/by-nc-nd/
Accession Number: edsbas.280A5CED
Database: BASE