Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
J Infect Dis. 2010 Jul 1;202(1):39-51. doi: 10.1086/653121.
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.
对于疫苗的开发，了解决定支原体呼吸道疾病耐药性和免疫病理学的调控机制至关重要。本研究评估了极化细胞因子干扰素γ（IFN-γ）和白细胞介素 4（IL-4）在调节支原体特异性免疫中的作用。单一细胞因子（IFN-γ或 IL-4）的缺失会独特地改变未感染小鼠肺部的多种趋化因子和细胞因子的表达，并影响对支原体感染的反应。最重要的是，IFN-γ（-/-）小鼠的鼻腔-肺免疫接种前导致支原体病加重，而免疫接种的 IL-4（-/-）小鼠比野生型小鼠显著更具抵抗力。IFN-γ（-/-）小鼠中的辅助性 T 细胞 2 型反应与支原体感染或免疫接种后发生的免疫病理反应相对应。因此，适应性免疫显然可以独立地促进支原体感染的保护或免疫病理学，而最佳的疫苗接种似乎依赖于促进保护性 IFN-γ依赖性网络（可能是辅助性 T 细胞 1 型反应），同时最小化 IL-4 介导的反应的影响，这些反应会抑制保护性免疫的产生。
