The Toll-Like Receptor 5 agonist flagellin prevents Non-typeable Haemophilus influenzae-induced infection in cigarette smoke-exposed mice

Abstract

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.

Endotypes of severe neutrophilic and eosinophilic asthma from multi‐omics integration of U‐BIOPRED sputum samples

“… 39 In contrast, some mouse studies suggest that IL‐22 may have both inflammatory and anti‐inflammatory effects in asthma 40 since administration of exogenous IL‐22 plays a protective role in an OVA‐induced asthma model. 41 A similar bidirectional effect of IL‐22 is seen in mouse models of COPD 42 although we have previously reported elevated levels of IL‐22 and IL‐22R mRNA and protein in the airways of mild‐to‐moderate COPD patients. In a mouse model pulmonary neutrophilic inflammation, airway remodelling and emphysema were reduced and lung function was improved in IL‐22 KO mice exposed to cigarette smoke compared to WT controls.…”

Lactobacillus plantarum surface-displayed Eimeria tenella profilin antigens with FliC flagellin elicit protection against coccidiosis in chickens

“…Overall, our results highlight the promising role of FliC as an effective adjuvant for enhancing immune responses and improving protective immunity against coccidiosis in chickens. The fusion of flagellin and antigen is a superior strategy compared to just mixing the 2 components, as they are recognized by the same APC and TLR5 during immunization ( Steiner, 2007 ; Pérez-Cruz et al, 2021 ).…”

Gut colonisation with multidrug-resistant Klebsiella pneumoniae worsens Pseudomonas aeruginosa lung infection

“…Cross-sections were stained by haematoxylin-eosin. To quantify lung lesions, a quantitative histopathologic score was used 42 .…”