TLR7 Promotes Acute Inflammatory-Driven Lung Dysfunction in Influenza-Infected Mice but Prevents Late Airway...

Area of Science:

• Immunology
• Respiratory Medicine
• Virology

Background:

• Severe lower respiratory tract disease from influenza A virus (IAV) involves excessive inflammation and lung damage.
• Toll-like receptor 7 (TLR7) detects viral RNA, initiating antiviral and inflammatory responses, but its role in IAV lung dysfunction is not fully understood.

Purpose of the Study:

• To investigate the role of toll-like receptor 7 (TLR7) in lung function and immune responses during influenza A virus (IAV) infection.
• To elucidate the dual function of TLR7 in acute and resolution phases of IAV-induced lung disease.

Main Methods:

• Utilized wild-type (WT) and TLR7 knockout (TLR7 KO) C57BL/6 mice infected with IAV.
• Assessed airway dysfunction, lung tissue mechanics, and immune cell infiltration at different time points post-infection.

Main Results:

• IAV infection caused airway dysfunction in both WT and TLR7 KO mice, but it manifested later and differently in TLR7 KO mice.
• Lung dysfunction correlated with neutrophils and Ly6C^lo monocytes in WT mice at day 7.
• TLR7 KO mice showed eosinophils and CD8+ T cells associated with airway hyperactivity at day 14, with higher IL-5 expression, suggesting a Th2 response.

Conclusions:

• TLR7 promotes inflammation-driven lung dysfunction during acute IAV infection.
• TLR7 deficiency suppresses eosinophilic and CD8+ T cell-mediated hyperresponsiveness during the resolution phase of IAV disease.
• TLR7 exhibits a dual role in IAV pathogenesis, impacting both acute inflammation and long-term lung function recovery.