title: Coinfection with Streptococcus pneumoniae modulates the B cell response to influenza virus.
abstract: Pathogen-specific antibodies (Abs) protect against respiratory infection with influenza A virus (IAV) and Streptococcus pneumoniae and are the basis of effective vaccines. Sequential or overlapping coinfections with both pathogens are common, yet the impact of coinfection on the generation and maintenance of Ab responses is largely unknown. We report here that the B cell response to IAV is altered in mice coinfected with IAV and S. pneumoniae and that this response differs, depending on the order of pathogen exposure. In mice exposed to S. pneumoniae prior to IAV, the initial virus-specific germinal center (GC) B cell response is significantly enhanced in the lung-draining mediastinal lymph node and spleen, and there is an increase in CD4(+) T follicular helper (TFH) cell numbers. In contrast, secondary S. pneumoniae infection exaggerates early antiviral antibody-secreting cell formation, and at later times, levels of GCs, TFH cells, and antiviral serum IgG are elevated. Mice exposed to S. pneumoniae prior to IAV do not maintain the initially robust GC response in secondary lymphoid organs and exhibit reduced antiviral serum IgG with diminished virus neutralization activity a month after infection. Our data suggest that the history of pathogen exposures can critically affect the generation of protective antiviral Abs and may partially explain the differential susceptibility to and disease outcomes from IAV infection in humans. Importance: Respiratory tract coinfections, specifically those involving influenza A viruses and Streptococcus pneumoniae, remain a top global health burden. We sought to determine how S. pneumoniae coinfection modulates the B cell immune response to influenza virus since antibodies are key mediators of protection.
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: Amaya I
authors.initials: AI
authors.lastname: Wolf
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: Maura C
authors.initials: MC
authors.lastname: Strauman
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Mozdzanowska
authors.affiliation: Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: James R R
authors.initials: JR
authors.lastname: Whittle
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Williams
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Arlene H
authors.initials: AH
authors.lastname: Sharpe
authors.affiliation: Department of Microbiology and Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Weiser
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Caton
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Hensley
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania, USA jan@wistar.org.
authors.forename: Jan
authors.initials: J
authors.lastname: Erikson
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D018858:Germinal Center; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000150:complications / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011008:Pneumococcal Infections / Q000150:complications / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*
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