Absence of Toll-like receptor 7 protects mice against Pseudomonas aeruginosa pneumonia

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Toll-like receptor 7 (TLR7) is a sensor of microbial ssRNA that participates in the immune response process in many diseases. We herein sought to establish the role of TLR7 in Pseudomonas aeruginosa pneumonia. Pneumonia model was created by intratracheally injecting Pseudomonas aeruginosa and the effects of TLR7 on survival, bacterial burden, lung pathology, cytokine and chemokine production, and pulmonary leukocyte recruitment were measured after Pseudomonas aeruginosa challenge. TLR7 expression was significantly elevated in WT mice after Pseudomonas aeruginosa infection. TLR7−/− mice demonstrated enhanced survival, bacterial clearance, leukocyte infiltration, and macrophages phagocytic activity, and decreased pathology and capillary leakage. Besides, improved survival and bacterial clearance were observed in WT mice treated with TLR7 antagonist IRS661. More importantly, lack of TLR7 suppressed pro-inflammatory cytokine production and induced anti-inflammatory cytokine production in mice lungs. Finally, neutralized IL-10 damaged the bacterial clearance ability of TLR7 deficient mice, leading to decreased survival. Collectively, absence of TLR7 provided protective effects during Pseudomonas aeruginosa pneumonia and suggested that TLR7 could act as a novel immune target to treat clinical cases with Pseudomonas aeruginosa pneumonia.