title: Capsules of virulent pneumococcal serotypes enhance formation of neutrophil extracellular traps during in vivo pathogenesis of pneumonia.
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.
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.
authors.forename: Anandi Narayana
authors.initials: AN
authors.lastname: Moorthy
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.|Infectious Diseases Interdisciplinary Research Group, Singapore-Massachusetts Institute of Technology Alliance in Research and Technology, Singapore.
authors.forename: Prashant
authors.initials: P
authors.lastname: Rai
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.
authors.forename: Huipeng
authors.initials: H
authors.lastname: Jiao
authors.affiliation: Department of Pathology, National University Hospital, Singapore.
authors.forename: Shi
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pathology, National University Hospital, Singapore.
authors.forename: Kong Bing
authors.initials: KB
authors.lastname: Tan
authors.affiliation: Department of Infection Control and Prevention, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Liang
authors.initials: L
authors.lastname: Qin
authors.affiliation: Department of Infection Control and Prevention, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, USA.
authors.forename: Narasaraju
authors.initials: N
authors.lastname: Teluguakula
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.|Infectious Diseases Interdisciplinary Research Group, Singapore-Massachusetts Institute of Technology Alliance in Research and Technology, Singapore.
authors.forename: Vincent Tak Kwong
authors.initials: VT
authors.lastname: Chow
mesh_terms: D000818:Animals; D016667:Bacterial Capsules / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D065206:Extracellular Traps / Q000276:immunology*; D005260:Female; D015870:Gene Expression / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008807:Mice, Inbred BALB C; D009154:Mutation; D009504:Neutrophils / Q000276:immunology*; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification / Q000235:genetics / Q000276:immunology*; D014774:Virulence / Q000235:genetics / Q000276:immunology
chemical_list: D016207:Cytokines
keywords: Immune response; Immunity; Immunology and Microbiology Section; Streptococcus pneumoniae; capsule; neutrophil extracellular traps; secondary pneumonia; serotype