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 journalArticle

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
JournalThe Journal of infectious diseases
Volume220
Issue number5
DOIs
StatePublished - Jul 31 2019

Fingerprint

Interleukin-17
Streptococcus pneumoniae
Orthomyxoviridae
Coinfection
Puerto Rico
Human Influenza
Nasopharyngeal Diseases
Nasopharynx
Influenza A virus
Inbred C57BL Mouse
Inflammation
Antibodies

Keywords

  • Streptococcus pneumoniae
  • coinfection
  • host response
  • IL17A
  • influenza

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Double-Edged Role of Interleukin 17A in Streptococcus pneumoniae Pathogenesis During Influenza Virus Coinfection. / Ambigapathy, Ganesh; Schmit, Taylor; Mathur, Ram Kumar; Nookala, Suba; Bahri, Saad; Pirofski, Liise-anne; Khan, M. Nadeem.

In: The Journal of infectious diseases, Vol. 220, No. 5, 31.07.2019, p. 902-912.

Research output: Contribution to journalArticle

Ambigapathy, Ganesh ; Schmit, Taylor ; Mathur, Ram Kumar ; Nookala, Suba ; Bahri, Saad ; Pirofski, Liise-anne ; Khan, M. Nadeem. / Double-Edged Role of Interleukin 17A in Streptococcus pneumoniae Pathogenesis During Influenza Virus Coinfection. In: The Journal of infectious diseases. 2019 ; Vol. 220, No. 5. pp. 902-912.
@article{2104dbcacb1f4304b665066da65d6005,
title = "Double-Edged Role of Interleukin 17A in Streptococcus pneumoniae Pathogenesis During Influenza Virus Coinfection",
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.",
keywords = "Streptococcus pneumoniae, coinfection, host response, IL17A, influenza",
author = "Ganesh Ambigapathy and Taylor Schmit and Mathur, {Ram Kumar} and Suba Nookala and Saad Bahri and Liise-anne Pirofski and Khan, {M. Nadeem}",
year = "2019",
month = "7",
day = "31",
doi = "10.1093/infdis/jiz193",
language = "English (US)",
volume = "220",
pages = "902--912",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "5",

}

TY - JOUR

T1 - Double-Edged Role of Interleukin 17A in Streptococcus pneumoniae Pathogenesis During Influenza Virus Coinfection

AU - Ambigapathy, Ganesh

AU - Schmit, Taylor

AU - Mathur, Ram Kumar

AU - Nookala, Suba

AU - Bahri, Saad

AU - Pirofski, Liise-anne

AU - Khan, M. Nadeem

PY - 2019/7/31

Y1 - 2019/7/31

N2 - 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.

AB - 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.

KW - Streptococcus pneumoniae

KW - coinfection

KW - host response

KW - IL17A

KW - influenza

UR - http://www.scopus.com/inward/record.url?scp=85070788797&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85070788797&partnerID=8YFLogxK

U2 - 10.1093/infdis/jiz193

DO - 10.1093/infdis/jiz193

M3 - Article

C2 - 31185076

AN - SCOPUS:85070788797

VL - 220

SP - 902

EP - 912

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 5

ER -