PT  - JOURNAL ARTICLE
AU  - Magdiel Pérez-Cruz
AU  - Bachirou Koné
AU  - Rémi Porte
AU  - Christophe Carnoy
AU  - Julien Tabareau
AU  - Pierre Gosset
AU  - François Trottein
AU  - Jean-Claude Sirard
AU  - Muriel Pichavant
AU  - Philippe Gosset
TI  - The Toll-Like Receptor 5 agonist flagellin prevents <em>Non-typeable Haemophilus influenzae</em>-induced exacerbations in cigarette smoke-exposed mice
AID  - 10.1101/2020.07.08.193128
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.07.08.193128
4099  - http://biorxiv.org/content/early/2020/07/08/2020.07.08.193128.short
4100  - http://biorxiv.org/content/early/2020/07/08/2020.07.08.193128.full
AB  - 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). 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 due to NTHi. Mice were chronically exposed to cigarette smoke and then infected with NTHi. According our preventive or therapeutic protocol, flagellin was administered intraperitoneally. 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. 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. Flagellin treatment also amplified the production of the β-defensin2 anti-bacterial peptides. This study shows that stimulation of innate immunity by a TLR5 ligand is a potent antibacterial treatment in cigarette smoke exposed mice, suggesting innovative therapeutic strategies against acute exacerbation in COPD.