Type I interferon induction during influenza virus infection increases susceptibility to secondary Streptococcus pneumoniae infection by negative regulation of γδ T cells

Wenjing Li, Bruno Moltedo, Thomas M. Moran

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

The majority of deaths following influenza virus infection result from secondary bacterial superinfection, most commonly caused by Streptococcus pneumoniae. Several models have been proposed to explain how primary respiratory viral infections exacerbate secondary bacterial disease, but the mechanistic explanations have beencontradictory. In this study, mice were infected with S. pneumoniae at different days after primary influenza A (X31) virus infection. Our findings show that the induction of type I interferons (IFNs) during a primary nonlethal influenza virus infection is sufficient to promote a deadly S. pneumoniae secondary infection. Moreover, mice deficient in type I interferon receptor (IFNAR knockout [KO] mice) effectively cleared the secondary bacterial infection from their lungs, increased the recruitment of neutrophils, and demonstrated an enhanced innate expression of interleukin-17 (IL-17) relative to wild-type (WT) mice. Lung γδ T cells were responsible for almost all IL-17 production, and their function is compromised during secondary S. pneumoniae infection of WT but not IFNAR KO mice. Adoptive transfer of γδ T cells from IFNAR KO mice reduced the susceptibility to secondary S. pneumoniae infection in the lung of WT mice. Altogether, our study highlightsthe importance of type I interferon as a key master regulator that is exploited by opportunistic pathogens such as S. pneumoniae. Our findings may be utilized to design effective preventive and therapeutic strategies that may be beneficial for coinfected patients during influenza epidemics.

Original languageEnglish
Pages (from-to)12304-12312
Number of pages9
JournalJournal of Virology
Volume86
Issue number22
DOIs
Publication statusPublished - Nov 2012
Externally publishedYes

Fingerprint

Pneumococcal Infections
Interferon Type I
Virus Diseases
Streptococcus pneumoniae
Orthomyxoviridae
Knockout Mice
T-Lymphocytes
Interleukin-17
Coinfection
Lung
Interferon alpha-beta Receptor
Superinfection
Adoptive Transfer
Neutrophil Infiltration
Influenza A virus
Bacterial Infections
Respiratory Tract Infections
Human Influenza
Therapeutics

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Type I interferon induction during influenza virus infection increases susceptibility to secondary Streptococcus pneumoniae infection by negative regulation of γδ T cells. / Li, Wenjing; Moltedo, Bruno; Moran, Thomas M.

In: Journal of Virology, Vol. 86, No. 22, 11.2012, p. 12304-12312.

Research output: Contribution to journalArticle

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