Abstract
Abstract Formyl peptide receptors (FPR) are playing a pivotal role in phagocyte migration in response to bacterial and host-derived chemoattractants. Despite their established roles, their involvement in immunity to tuberculosis remains unexplored. In this study, we investigated the contributions of Fpr1 and Fpr2 to host defense against Mycobacterium tuberculosis (Mtb) infection. Fpr1 and Fpr2 expression increased in the lungs of rabbits as early as 3 hours and remained elevated during the chronic phase of infection. Additionally, these receptors were increasingly expressed in neutrophils of mice highly susceptible to infection, implying a potential role in the host response to Mtb. We assessed bacterial burden, lung damage, and cellular inflammation following infection of Fpr1-/- and Fpr2-/- mice with a hypervirulent W-Beijing lineage strain of Mtb. While Fpr2 deletion exhibited no discernible impact on host resistance, Fpr1 deficiency compromised bacterial control in the lungs. This effect was particularly pronounced in genetically susceptible mice treated with Fpr1-specific inhibitors. In vitro experiments demonstrated that bone marrow–derived neutrophils and macrophages lacking Fpr1 were incapable of controlling intracellular Mtb growth. Collectively, our findings underscore the differential roles of Fpr1 and Fpr2 in the host defense against Mtb infection, highlighting Fpr1 as a potential therapeutic target for enhancing immune responses against tuberculosis.
Published Version
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