Year: 2024
Type: article
Abstract: Host-directed therapy, using nasal administration of the Toll-like receptor 5 agonist flagellin in combination with antibiotics, has proven effective against pneumococcal pneumonia. In this study, we investigated the immune mechanisms underlying the therapy-induced protective effects. Transcriptomic analysis of lung tissue during infection revealed that flagellin not only enhanced pathways associated with myeloid cell infiltration into the airways and antimicrobial functions, but also promoted the early and transient mobilization of neutrophils and inflammatory monocytes. Neutrophils were identified as crucial for the protective effects of flagellin. The adjunct activity of flagellin correlated with the increased recruitment of neutrophils into airways, their localization at the periphery of bronchi, alveoli, and lung vessels, along with alterations in phagocytic activity. Clustering analysis identified seven neutrophil subsets; notably, flagellin adjunct treatment expanded clusters involved in recruitment and antibacterial activity, and primed augmented functionality. In conclusion, this study highlights specific neutrophil subsets as a promising target for host-directed therapy in infection.
Source: Mucosal Immunology
Institutions: Centre National de la Recherche Scientifique, Inserm, Université de Lille, Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Centre Hospitalier Universitaire de Lille, Plateformes Lilloises en Biologie et Santé, European Genomic Institute for Diabetes, (Epi)génomique fonctionnelle métabolique et des dysfonctions dans le diabète de type 2 et des maladies associées, Institut Gustave Roussy
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,800
Awards: Boosting respiratory innate immunity to treat pneumonia caused by antibiotic-resistant bacteria, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique, FLAGELLIN AEROSOL THERAPY AS AN IMMUNOMODULATORY ADJUNCT TO THE ANTIBIOTIC TREATMENT OF DRUG-RESISTANT BACTERIAL PNEUMONIA, Plate forme Lilloise de séquençage du génome humain pour une médecine personnalisée, Repurposing disused antibiotics with immune modulators as antimicrobial strategy for respiratory tract infections
OpenAlex ID: W4404665709