title: Influenza A Virus Infection Predisposes Hosts to Secondary Infection with Different Streptococcus pneumoniae Serotypes with Similar Outcome but Serotype-Specific Manifestation.
abstract: Influenza A virus (IAV) and Streptococcus pneumoniae are major causes of respiratory tract infections, particularly during coinfection. The synergism between these two pathogens is characterized by a complex network of dysregulated immune responses, some of which last until recovery following IAV infection. Despite the high serotype diversity of S. pneumoniae and the serotype replacement observed since the introduction of conjugate vaccines, little is known about pneumococcal strain dependency in the enhanced susceptibility to severe secondary S. pneumoniae infection following IAV infection. Thus, we studied how preinfection with IAV alters host susceptibility to different S. pneumoniae strains with various degrees of invasiveness using a highly invasive serotype 4 strain, an invasive serotype 7F strain, and a carrier serotype 19F strain. A murine model of pneumococcal coinfection during the acute phase of IAV infection showed a significantly increased degree of pneumonia and mortality for all tested pneumococcal strains at otherwise sublethal doses. The incidence and kinetics of systemic dissemination, however, remained bacterial strain dependent. Furthermore, we observed strain-specific alterations in the pulmonary levels of alveolar macrophages, neutrophils, and inflammatory mediators ultimately affecting immunopathology. During the recovery phase following IAV infection, bacterial growth in the lungs and systemic dissemination were enhanced in a strain-dependent manner. Altogether, this study shows that acute IAV infection predisposes the host to lethal S. pneumoniae infection irrespective of the pneumococcal serotype, while the long-lasting synergism between IAV and S. pneumoniae is bacterial strain dependent. These results hold implications for developing tailored therapeutic treatment regimens for dual infections during future IAV outbreaks.
authors.affiliation: Immune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.|Infection Immunology Group, Institute of Medical Microbiology, Infection Prevention and Control, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Niharika
authors.initials: N
authors.lastname: Sharma-Chawla
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Vicky
authors.initials: V
authors.lastname: Sender
authors.affiliation: Department of Veterinary Medicine, Institute of Veterinary Pathology, Free University Berlin, Berlin, Germany.
authors.forename: Olivia
authors.initials: O
authors.lastname: Kershaw
authors.affiliation: Department of Veterinary Medicine, Institute of Veterinary Pathology, Free University Berlin, Berlin, Germany.
authors.forename: Achim D
authors.initials: AD
authors.lastname: Gruber
authors.affiliation: Immune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Volckmar
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.|Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Henriques-Normark
authors.affiliation: Immune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany Sabine.Stegemann-Koniszewski@helmholtz-hzi.de Dunja.Bruder@med.ovgu.de.|Infection Immunology Group, Institute of Medical Microbiology, Infection Prevention and Control, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Stegemann-Koniszewski
authors.affiliation: Immune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany Sabine.Stegemann-Koniszewski@helmholtz-hzi.de Dunja.Bruder@med.ovgu.de.|Infection Immunology Group, Institute of Medical Microbiology, Infection Prevention and Control, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Dunja
authors.initials: D
authors.lastname: Bruder
mesh_terms: D000818:Animals; D060085:Coinfection; D005260:Female; D007113:Immunity, Innate; D009980:Influenza A virus; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000150:complications / Q000401:mortality / Q000821:virology*; D011008:Pneumococcal Infections / Q000150:complications / Q000276:immunology / Q000382:microbiology* / Q000401:mortality; D065288:Serogroup; D013296:Streptococcus pneumoniae / Q000145:classification* / Q000502:physiology; D019562:Viral Load