Vincent TK Chow
University of Singapore, Singapore
Title: The importance of neutrophil extracellular traps and vascular leakage in pneumonia caused by influenza virus and pneumococcus
Biography
Biography: Vincent TK Chow
Abstract
Excessive host inflammatory responses negatively impact disease outcomes of pneumonia. To better understand host-pathogen interactions during the critical inflammatory and repair phases of pneumonia, we investigated the role of neutrophils, neutrophil extracellular traps (NETs) and c-angiopoietin-like 4 (cANGPTL4) in the pathogenesis of influenza and pneumococcal pneumonia. The presence of NETs and the effects of cANGPTL4 were studied in mouse models of primary infection with influenza virus H1N1 and/or H3N2, and secondary pneumococcal pneumonia. Excessive infiltration of neutrophils and
significant formation of NETs were associated with severe influenza and pneumococcal pneumonia. Intense pulmonary NETs generation, elevated myeloperoxidase activity, cytokine dysregulation, pneumococcal capsule thickness determined the disease severity. Influenza infection stimulated the expression of cANGPTL4 via a direct mechanism mediated by interleukin-6 and STAT3. cANGPTL4 enhanced pulmonary tissue leakiness and exacerbated inflammation-induced lung injury. Treatment of infected mice with neutralizing anti-cANGPTL4 antibody significantly accelerated lung recovery and enhanced lung tissue integrity. The cANGPTL4-deficient mice also displayed diminished lung damage and recovered more rapidly from influenza pneumonia compared to their wild-type counterparts. Retrospective examination of lung biopsies and clinical samples from patients with infection-induced pneumonia with tissue damage revealed elevated expression of cANGPTL4 compared to normal or uninfected samples. These observations highlight the important roles that NETs and cANGPTL4 play in pulmonary infection and damage, and may facilitate the development of novel biomarkers and intervention strategies to improve the management of pneumonia. From the infection control perspective, the research also emphasizes the clinical importance of improving the coverage of influenza and pneumococcal vaccination especially among high-risk individuals.