The contribution of interleukin-12/interferon-γ axis in protection against neonatal pulmonary chlamydia muridarum challenge

Madhulika Jupelli, Dale M. Selby, M. Neal Guentzel, James P. Chambers, Thomas G. Forsthuber, Guangming Zhong, Ashlesh K. Murthy, Bernard P. Arulanandam

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Neonatal Chlamydia trachomatis pneumonia has been associated with respiratory sequelae in later life. We recently established a mouse model of neonatal pulmonary Chlamydia muridaum infection and found an important contribution of IFN-γ to protective immunity. In this study, we further characterized the role of Th1-type cytokines; IL-12, IFN-γ, and IFN-γ signaling using mice genetically deficient in IL-12, IFN-γ, or IFN-γ receptor 1. All 3 knockout (KO) mice challenged intranasally with C. muridarum 1 day after birth exhibited 100% mortality by day 17 post-challenge whereas wild-type (WT) animals survived the monitoring period of 1 month. The KO mice exhibited greater lung bacterial burdens and enhanced dissemination to the liver, compared to WT animals. The inflammatory cellular infiltration in C. muridarum-challenged KO animals was significantly reduced in the lungs, but markedly enhanced in the livers of the KO mice compared to similarly challenged WT mice. It was also found that a deficiency in IL-12 or IFN-γ resulted in correspondingly reduced IFN-γ or IL-12 production, respectively, suggesting an intricate interdependence in the induction of these cytokines. Collectively, these results suggest that the IL-12/ IFN-γ axis induces pulmonary cellular infiltration, induces bacterial clearance from the lung, reduces dissemination to other organs, and promotes the survival of the host during neonatal pulmonary chlamydial infection.

Original languageEnglish (US)
Pages (from-to)407-415
Number of pages9
JournalJournal of Interferon and Cytokine Research
Volume30
Issue number6
DOIs
StatePublished - Jun 1 2010

ASJC Scopus subject areas

  • Immunology
  • Cell Biology
  • Virology

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