The Toll-Like Receptor 5 agonist flagellin prevents Non-typeable Haemophilus influenzae-induced infection in cigarette smoke-exposed mice
| Autor: | Pérez-Cruz, Magdiel, Koné, Bachirou, Porte, Rémi, Carnoy, Christophe, Tabareau, Julien, Gosset, Pierre, Trottein, François, Sirard, Jean-Claude, Pichavant, Muriel, Gosset, Philippe |
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| Přispěvatelé: | Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Hôpital Saint Vincent de Paul de Lille, Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), Conseil Régional du Nord-Pas de Calais StreptoCOPD project, grant number # 13005300, Institut National de la Santé et de la Recherche Médicale (Inserm), Centre National de la Recherche Scientifique (CNRS), University of Lille, Sirard, Jean-Claude, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Pulmonology Physiology Neutrophils [SDV]Life Sciences [q-bio] Cancer Treatment Biochemistry White Blood Cells Mice Pulmonary Disease Chronic Obstructive Animal Cells Microbial Physiology Immune Physiology Smoke Medicine and Health Sciences Bacterial Physiology Immune Response Lung Mice Knockout Innate Immune System Recombinant Proteins Body Fluids Up-Regulation [SDV] Life Sciences [q-bio] Blood Oncology Cytokines Medicine Cellular Types Anatomy Research Article Haemophilus Infections Chronic Obstructive Pulmonary Disease Immune Cells Science Immunology Cytokine Therapy Microbiology Signs and Symptoms Tobacco Animals Inflammation Blood Cells Interleukins Biology and Life Sciences Proteins Bacteriology Cell Biology Molecular Development Haemophilus influenzae Mice Inbred C57BL Toll-Like Receptor 5 Immune System Clinical Medicine Spleen Flagellin Developmental Biology Antimicrobial Cationic Peptides |
| Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2021, 16 (3), ⟨10.1371/journal.pone.0236216⟩ PLoS ONE, Vol 16, Iss 3, p e0236216 (2021) PLoS ONE, 2021, 16 (3), ⟨10.1371/journal.pone.0236216⟩ |
| ISSN: | 1932-6203 |
| Popis: | Corresponding author: Philippe Gosset (philippe.gosset@pasteur-lille.fr); International audience; Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. The major bacterial cause of COPD exacerbations is non-typeable Haemophilus influenzae (NTHi). 25 to over 80% of cases are associated with NTHi. This susceptibility to infection involves a defective production of interleukin (IL)-22 which plays an important role in mucosal defense. Prophylactic administration of flagellin, a Toll-like receptor 5 (TLR5) agonist, protects healthy mice against respiratory pathogenic bacteria. We hypothesized that TLR5-mediated stimulation of lung immunity might prevent COPD exacerbations. Mice chronically exposed to cigarette smoke (CS), which presented COPD symptoms, were infected with NTHi and intraperitoneally treated with recombinant flagellin following a prophylactic or therapeutic protocol. Compared with control, cigarette smoke-exposed mice treated with flagellin showed a lower bacterial load in the airways, the lungs and the blood. This protection was associated with an early neutrophilia, a lower production of pro-inflammatory cytokines and an increased IL-22 production. Flagellin treatment decreased the recruitment of inflammatory cells and the lung damages related to exacerbation. Morover, the protective effect of flagellin against NTHi was altered by treatment with anti-IL-22 blocking antibodies in cigarette smoke-exposed mice and in Il22 -/- mice. The effect of flagellin treatment did not implicated the anti-bacterial peptides calgranulins and defensin-β2. This study shows that stimulation of innate immunity by a TLR5 ligand is a potent antibacterial treatment in CS-exposed mice, suggesting innovative therapeutic strategies against acute exacerbation in COPD. |
| Databáze: | OpenAIRE |
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