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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\n            <jats:named-content content-type=\"genus-species\">S. pneumoniae<\/jats:named-content>\n            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\n            <jats:named-content content-type=\"genus-species\">S. pneumoniae<\/jats:named-content>\n            infection following IAV infection. Thus, we studied how preinfection with IAV alters host susceptibility to different\n            <jats:named-content content-type=\"genus-species\">S. pneumoniae<\/jats:named-content>\n            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\n            <jats:named-content content-type=\"genus-species\">S. pneumoniae<\/jats:named-content>\n            infection irrespective of the pneumococcal serotype, while the long-lasting synergism between IAV and\n            <jats:named-content content-type=\"genus-species\">S. pneumoniae<\/jats:named-content>\n            is bacterial strain dependent. These results hold implications for developing tailored therapeutic treatment regimens for dual infections during future IAV outbreaks.\n          <\/jats:p>","DOI":"10.1128\/iai.00422-16","type":"journal-article","created":{"date-parts":[[2016,9,20]],"date-time":"2016-09-20T01:50:07Z","timestamp":1474336207000},"page":"3445-3457","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":60,"title":["Influenza A Virus Infection Predisposes Hosts to Secondary Infection with Different Streptococcus pneumoniae Serotypes with Similar Outcome but Serotype-Specific Manifestation"],"prefix":"10.1128","volume":"84","author":[{"given":"Niharika","family":"Sharma-Chawla","sequence":"first","affiliation":[{"name":"Immune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany"},{"name":"Infection Immunology Group, Institute of Medical Microbiology, Infection Prevention and Control, Otto-von-Guericke University, Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicky","family":"Sender","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Kershaw","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, Institute of Veterinary Pathology, Free University Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim D.","family":"Gruber","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, Institute of Veterinary Pathology, Free University Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Volckmar","sequence":"additional","affiliation":[{"name":"Immune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgitta","family":"Henriques-Normark","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Stegemann-Koniszewski","sequence":"additional","affiliation":[{"name":"Immune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany"},{"name":"Infection Immunology Group, Institute of Medical Microbiology, Infection Prevention and Control, Otto-von-Guericke University, Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dunja","family":"Bruder","sequence":"additional","affiliation":[{"name":"Immune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany"},{"name":"Infection Immunology Group, Institute of Medical Microbiology, Infection Prevention and Control, Otto-von-Guericke University, Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1209.05-0979"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc0908216"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3231"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.4161\/21645515.2014.979631"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00116.2016"},{"key":"e_1_3_3_7_2","first-page":"93","article-title":"Pneumococcal conjugate vaccine for childhood immunization\u2014WHO position paper","volume":"82","year":"2007","unstructured":". 2007. 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