1. A Pulmonary Lactobacillus murinus Strain Induces Th17 and RORγt + Regulatory T Cells and Reduces Lung Inflammation in Tuberculosis
- Author
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Bernard-Raichon, Lucie, Colom, André, Monard, Sarah, Namouchi, Amine, Cescato, Margaux, Garnier, Hugo, Leon-Icaza, Stephen, Métais, Arnaud, Dumas, Alexia, Corral, Dan, Ghebrendrias, Natsinet, Guilloton, Pauline, Vérollet, Christel, Hudrisier, Denis, Remot, Aude, Langella, Philippe, Thomas, Muriel, Cougoule, Céline, Neyrolles, Olivier, Lugo-Villarino, Geanncarlo, Marín Franco, José Luis, Genoula, Melanie, Duette, Gabriel, Ferreyra, Malena, Maio, Mariano, Dolotowicz, María Belén, Aparicio-Trejo, Omar Emiliano, Patiño-Martínez, Eduardo, Charton, Alison, Fuentes, Federico, Soldan, Vanessa, Moraña, Eduardo José, Palmero, Domingo, Ostrowski, Matías, Schierloh, Pablo, Sánchez-Torres, Carmen, Hernández-Pando, Rogelio, Pedraza-Chaverri, José, Rombouts, Yoann, Layre, Emilie, Maridonneau-Parini, Isabelle, Sasiain, María del Carmen, Balboa, Luciana, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre for Ecological and Evolutionary Synthesis (CEES), Department of Biosciences [Oslo], Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Norwegian University of Life Sciences (NMBU), 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 (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CNRS, Fondation pour la Recherche Medicale (DEQ2016 0334894, FDT201805005210), Fondation Bettencourt Schueller, ANR-15-CE15-0012,MMI-TB,Rôle du microbiome dans la réponse des macrophages à Mycobacterium tuberculosis: un programme de recherche intégrant le microbiote, le métabolisme et l'immunité(2015), ANR-18-CE15-0004,GENDER-TB,Bases immunologiques de la susceptibilité différentielle des genres à la tuberculose(2018), and European Project: 267196,EC:FP7:PEOPLE,FP7-PEOPLE-2010-COFUND,AGREENSKILLS(2012)
- Subjects
Tuberculosis ,Regulatory T cell ,T cell ,[SDV]Life Sciences [q-bio] ,Immunology ,Inflammation ,Mycobacterium tuberculosis ,03 medical and health sciences ,0302 clinical medicine ,Immunity ,RAR-related orphan receptor gamma ,Immunology and Allergy ,Medicine ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,0303 health sciences ,Lung ,biology ,business.industry ,biology.organism_classification ,medicine.disease ,3. Good health ,medicine.anatomical_structure ,medicine.symptom ,business ,030215 immunology - Abstract
The lungs harbor multiple resident microbial communities, otherwise known as the microbiota. There is an emerging interest in deciphering whether the pulmonary microbiota modulate local immunity, and whether this knowledge could shed light on mechanisms operating in the response to respiratory pathogens. In this study, we investigate the capacity of a pulmonary Lactobacillus strain to modulate the lung T cell compartment and assess its prophylactic potential upon infection with Mycobacterium tuberculosis, the etiological agent of tuberculosis. In naive mice, we report that a Lactobacillus murinus (Lagilactobacillus murinus) strain (CNCM I-5314) increases the presence of lung Th17 cells and of a regulatory T cell (Treg) subset known as RORγt+ Tregs. In particular, intranasal but not intragastric administration of CNCM I-5314 increases the expansion of these lung leukocytes, suggesting a local rather than systemic effect. Resident Th17 and RORγt+ Tregs display an immunosuppressive phenotype that is accentuated by CNCM I-5314. Despite the well-known ability of M. tuberculosis to modulate lung immunity, the immunomodulatory effect by CNCM I-5314 is dominant, as Th17 and RORγt+ Tregs are still highly increased in the lung at 42-d postinfection. Importantly, CNCM I-5314 administration in M. tuberculosis–infected mice results in reduction of pulmonary inflammation, without increasing M. tuberculosis burden. Collectively, our findings provide evidence for an immunomodulatory capacity of CNCM I-5314 at steady state and in a model of chronic inflammation in which it can display a protective role, suggesting that L. murinus strains found in the lung may shape local T cells in mice and, perhaps, in humans.
- Published
- 2021