Capsules of virulent pneumococcal serotypes enhance formation of neutrophil extracellular traps during <i>in vivo</i> pathogenesis of pneumonia

Abstract

// Anandi Narayana Moorthy 1 , Prashant Rai 1,2 , Huipeng Jiao 1 , Shi Wang 3 , Kong Bing Tan 3 , Liang Qin 4 , Hiroshi Watanabe 4 , Yongliang Zhang 1 , Narasaraju Teluguakula 5 and Vincent Tak Kwong Chow 1,2 1 Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore 2 Infectious Diseases Interdisciplinary Research Group, Singapore-Massachusetts Institute of Technology Alliance in Research and Technology, Singapore 3 Department of Pathology, National University Hospital, Singapore 4 Department of Infection Control and Prevention, Kurume University School of Medicine, Fukuoka, Japan 5 Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, USA Correspondence to: Vincent Tak Kwong Chow, email: // Keywords : neutrophil extracellular traps, Streptococcus pneumoniae, capsule, serotype, secondary pneumonia, Immunology and Microbiology Section, Immune response, Immunity Received : December 30, 2015 Accepted : March 18, 2016 Published : March 28, 2016 Abstract Neutrophil extracellular traps (NETs) are released by activated neutrophils to ensnare and kill microorganisms. NETs have been implicated in tissue injury since they carry cytotoxic components of the activated neutrophils. We have previously demonstrated the generation of NETs in infected murine lungs during both primary pneumococcal pneumonia and secondary pneumococcal pneumonia after primary influenza. In this study, we assessed the correlation of pneumococcal capsule size with pulmonary NETs formation and disease severity. We compared NETs formation in the lungs of mice infected with three pneumococcal strains of varying virulence namely serotypes 3, 4 and 19F, as well as a capsule-deficient mutant of serotype 4. In primary pneumonia, NETs generation was strongly associated with the pneumococcal capsule thickness, and was proportional to the disease severity. Interestingly, during secondary pneumonia after primary influenza infection, intense pulmonary NETs generation together with elevated myeloperoxidase activity and cytokine dysregulation determined the disease severity. These findings highlight the crucial role played by the size of pneumococcal capsule in determining the extent of innate immune responses such as NETs formation that may contribute to the severity of pneumonia.