Innate Immune Response of Blood Cells in Patients With Pneumonia

Overview

Pulmonary bacterial infections such as exacerbations of chronic bronchitis, nosocomial and community-acquired pneumonia represent a major public health issue. Antibiotics have shown their efficacy by direct antimicrobial activity and their limit particularly in case of multidrug-resistant microorganisms or in treating patients with aggravating pathologies. Innate immunity could be an alternative or complementary therapeutic pathway. Innate immunity receptors bind universal and invariant microbial molecular patterns present in bacteria, virus, fungus or parasite. Toll-like Receptors (TLR) activation by microbial agonist stimulates the innate immunity response which results in the production of chemokines, cytokines, antimicrobial molecules and the recruitment of innate cells. The " Pulmonary Infection and Innate Immunity " team of the Immunity and Infection Center in Lille (Group of Dr. Sirard and Carnoy) has a long expertise in the study of TLR5 and its agonist, the flagellin, a structural protein of bacterial flagella. TLR5 is expressed on the cell surface of macrophages, monocytes, dendritic and epithelial cells. Several studies in mice have shown the flagellin prophylactic potential during bacterial infections through a TLR5 dependent stimulation of innate immunity. Recently, the group of Dr. Sirard and Carnoy has shown that flagellin can be used in association with antibiotics to treat Streptococcus pneumoniae respiratory infections in mice. The results demonstrate that an agonist of TLR can increase the therapeutic index of an antibiotic and improve the pulmonary anti-infectious reaction. This innovative approach allows us to consider new antibacterial strategies where antibiotics have reached their limit (nosocomial infection, multidrug-resistant bacteria…). TLR agonists can activate multiple human cell type. Indeed, blood cells activation by TLR agonists have been recently characterized in healthy volunteers. However, there is no available data on the ability of TLR agonists to activate cells from patients with infectious pneumopathies. A study in these patients is inevitable if one is to consider the therapeutic use of agonists in respiratory pathologies.

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