title: Interferon gamma and interleukin 4 have contrasting effects on immunopathology and the development of protective adaptive immunity against mycoplasma respiratory disease.
abstract: For vaccine development, it is critical to understand the regulatory mechanisms determining resistance and immunopathology against mycoplasma respiratory diseases. The present study evaluated the contribution of the polarizing cytokines interferon gamma (IFN-gamma) and interleukin 4 (IL-4) in the regulation of mycoplasma-specific immunity. The absence of a single cytokine (either IFN-gamma or IL-4) uniquely altered the expression of multiple chemokines and cytokines in the lungs of uninfected mice and influenced responses to mycoplasma infection. Most importantly, prior nasal-pulmonary immunization of IFN-gamma(-/-) mice led to exacerbated mycoplasma disease, whereas immunized IL-4(-/-) mice were dramatically more resistant than wild-type mice. Helper T cell type 2 responses in IFN-gamma(-/-) mice corresponded to immunopathologic reactions that developed after mycoplasma infection or immunization. Thus, adaptive immunity clearly can independently promote either protection or immunopathology against mycoplasma infection, and optimal vaccination appears to be dependent on promoting protective IFN-gamma-dependent networks (perhaps helper T cell type 1 responses) while minimizing the effect of IL-4-mediated responses, which dampen the generation of protective immunity.
authors.affiliation: Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
authors.forename: Sheetal
authors.initials: S
authors.lastname: Bodhankar
authors.forename: Xiangle
authors.initials: X
authors.lastname: Sun
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Woolard
authors.forename: Jerry W
authors.initials: JW
authors.lastname: Simecka
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009175:Mycoplasma Infections / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000382:microbiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020381:Interleukin-17; D015848:Interleukin-5; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma