Double-edged role of interleukin 17a in streptococcus pneumoniae pathogenesis during influenza virus coinfection

Ganesh Ambigapathy, Taylor Schmit, Ram Kumar Mathur, Suba Nookala, Saad Bahri, Liise Anne Pirofski, M. Nadeem Khan

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Background: We sought to determine the role of host interleukin 17A (IL-17A) response against colonizing Streptococcus pneumoniae, and its transition to a pathogen during coinfection with an influenza virus, influenza A H1N1 A/Puerto Rico/8/1934 (PR8). Method: Wild-type (WT) C57BL/6 mice were intranasally inoculated with S. pneumoniae serotype 6A to establish colonization and later infected with the influenza strain, PR8, resulting in invasive S. pneumoniae disease. The role of the IL-17A response in colonization and coinfection was investigated in WT, RoRγt-/- and RAG1-/- mice with antibody-mediated depletion of IL-17A (WT) and CD90 cells (RAG1-/-). Results: RAG1-/- mice did not clear colonization and IL-17A neutralization impaired 6A clearance in WT mice. RoRγt-/- mice also had reduced clearance. S. pneumoniae-PR8 coinfection elicited a robust IL-17A response in the nasopharynx; IL-17A neutralization reduced S. pneumoniae invasive disease. RoRγt-/- mice also had reduced S. pneumoniae disease in a coinfection model. Depletion of CD90+ cells suppressed the IL-17A response and reduced S. pneumoniae invasion in RAG1-/- mice. Conclusion: Our data show that although IL-17A reduces S. pneumoniae colonization, coinfection with influenza virus elicits a robust innate IL-17A response that promotes inflammation and S. pneumoniae disease in the nasopharynx.

Original languageEnglish (US)
Pages (from-to)902-912
Number of pages11
JournalJournal of Infectious Diseases
Volume220
Issue number5
DOIs
StatePublished - Jul 31 2019

Keywords

  • Coinfection
  • Host response
  • Il17a
  • Influenza
  • Streptococcus pneumoniae

ASJC Scopus subject areas

  • General Medicine

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