title: Lethal coinfection of influenza virus and Streptococcus pneumoniae lowers antibody response to influenza virus in lung and reduces numbers of germinal center B cells, T follicular helper cells, and plasma cells in mediastinal lymph Node.
abstract: Secondary Streptococcus pneumoniae infection after influenza is a significant clinical complication resulting in morbidity and sometimes mortality. Prior influenza virus infection has been demonstrated to impair the macrophage and neutrophil response to the subsequent pneumococcal infection. In contrast, how a secondary pneumococcal infection after influenza can affect the adaptive immune response to the initial influenza virus infection is less well understood. Therefore, this study focuses on how secondary pneumococcal infection after influenza may impact the humoral immune response to the initial influenza virus infection in a lethal coinfection mouse model. Compared to mice infected with influenza virus alone, mice coinfected with influenza virus followed by pneumococcus had significant body weight loss and 100% mortality. In the lung, lethal coinfection significantly increased virus titers and bacterial cell counts and decreased the level of virus-specific IgG, IgM, and IgA, as well as the number of B cells, CD4 T cells, and plasma cells. Lethal coinfection significantly reduced the size and weight of spleen, as well as the number of B cells along the follicular developmental lineage. In mediastinal lymph nodes, lethal coinfection significantly decreased germinal center B cells, T follicular helper cells, and plasma cells. Adoptive transfer of influenza virus-specific immune serum to coinfected mice improved survival, suggesting the protective functions of anti-influenza virus antibodies. In conclusion, coinfection reduced the B cell response to influenza virus. This study helps us to understand the modulation of the B cell response to influenza virus during a lethal coinfection.
  
  
  OBJECTIVE
  Secondary pneumococcal infection after influenza virus infection is an important clinical issue that often results in excess mortality. Since antibodies are key mediators of protection, this study aims to examine the antibody response to influenza virus and demonstrates that lethal coinfection reduced the B cell response to influenza virus. This study helps to highlight the complexity of the modulation of the B cell response in the context of coinfection.
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Yuet
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China wwtu@hku.hk lauylung@hkucc.hku.hk.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Tu
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Kwok-Tai
authors.initials: KT
authors.lastname: Lam
authors.affiliation: Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Kin-Hung
authors.initials: KH
authors.lastname: Chow
authors.affiliation: Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Pak-Leung
authors.initials: PL
authors.lastname: Ho
authors.affiliation: Centre of Influenza Research, School of Public Health, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Centre of Influenza Research, School of Public Health, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Joseph S Malik
authors.initials: JS
authors.lastname: Peiris
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China wwtu@hku.hk lauylung@hkucc.hku.hk.
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lau
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D060085:Coinfection / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D004195:Disease Models, Animal; D005260:Female; D018858:Germinal Center; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D008198:Lymph Nodes / Q000276:immunology*; D008810:Mice, Inbred C57BL; D009975:Orthomyxoviridae / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000150:complications* / Q000276:immunology*; D010950:Plasma Cells / Q000276:immunology; D011018:Pneumonia, Pneumococcal / Q000150:complications* / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology; D016019:Survival Analysis; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology