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IFN‐γ and IL‐4 have opposing effects on immunopathology and the development protective adaptive immunity against mycoplasma respiratory disease
Author(s) -
Bodhankar Sheetal,
Sun Xiangle,
Woolard Matthew D,
Simecka Jerry W
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.513
Subject(s) - interleukin 4 , immunity , immunology , cytokine , immune system , biology , acquired immune system , immunopathology , mycoplasma , innate immune system , interferon gamma , microbiology and biotechnology
Murine mycoplasma disease progression is dependent on host immune responses. IFNγ is critical in developing beneficial innate immunity. Lack of IFNγ impairs the ability to control infection whereas loss of IL4 does not. The purpose of this study was to discern whether the loss of either IFNγ or IL4 altered, the cytokine cascade after infection & the generation of adaptive immunity against mycoplasma. Cytokine mRNA expression was monitored in M. pulmonis infected wild‐type, IFNγ & IL4 KO BALB/c mice using microarrays. The lungs of naïve IFNγ & IL4 KO mice had Th2 & Th1 dominant cytokine mRNA profiles, respectively. There was a significant increase in pro‐inflammatory cytokine mRNA expression in infected IFNγ KO mice compared to WT, along with severe disease. Whereas, these mRNA levels were lower in the lungs of IL4 KO mice than the WT mice. In vitro T cell responses were consistent with mRNA profiles. To examine generation of protective immunity, nasal pulmonary immunized WT & KO mice were challenged & mycoplasma numbers determined in the nasal passages (NP) & lungs. Immunized IFNγ KO mice had severe lesions & higher numbers of mycoplasma in both NP & lungs than WT. In contrast, the IL4 KO mice were significantly better protected than the immunized WT mice. In conclusion, IFNγ is critical in reducing the development of immunopathology & mediating immune protection whereas IL4 has the opposite effect.