Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, PA 16802, USA.
J Immunol. 2010 Feb 1;184(3):1392-400. doi: 10.4049/jimmunol.0803045. Epub 2009 Dec 30.
Bordetella parapertussis causes the prolonged coughing illness known as pertussis or whooping cough, persisting for weeks within the respiratory tracts of infected hosts but inducing a very poor T cell response relative to that induced by Bordetella pertussis, the more common cause of pertussis. In this study, we examine the contributions of cytokines involved in the clearance of B. parapertussis and immunomodulation that delays effective clearance. The slow elimination of this pathogen from the respiratory tracts of mice coincides with the gradual accumulation of CD4(+) T cells in the lungs and B. parapertussis-responsive IFN-gamma-producing cells in the spleen. IFN-gamma-deficient mice were defective in the accumulation of leukocytes in lungs and in clearance of B. parapertussis from the lungs. In vitro B. parapertussis-stimulated macrophages produced IL-10, which inhibited the generation of the IFN-gamma response that is required for protection in vivo. As compared with wild-type mice, IL-10-deficient mice produced significantly higher levels of IFN-gamma, had higher numbers of leukocytes accumulated in the lungs, and cleared B. parapertussis more rapidly. Together, these data indicate that B. parapertussis induces the production of IL-10, which facilitates its persistence within infected hosts by limiting a protective IFN-gamma response.
百日咳博德特氏菌引起的长时间咳嗽病，称为百日咳或痉咳，在感染宿主的呼吸道内持续数周，但相对于更常见的百日咳博德特氏菌引起的痉咳，其诱导的 T 细胞反应非常差。在这项研究中，我们研究了参与百日咳博德特氏菌清除和免疫调节的细胞因子的作用，这些免疫调节会延迟有效的清除。这种病原体从老鼠呼吸道中缓慢清除，与肺部 CD4(+) T 细胞和脾脏中对百日咳博德特氏菌有反应的 IFN-γ产生细胞的逐渐积累相一致。IFN-γ缺陷型小鼠在肺部白细胞的积累和百日咳博德特氏菌从肺部的清除方面存在缺陷。体外百日咳博德特氏菌刺激的巨噬细胞产生了 IL-10，抑制了体内保护所需的 IFN-γ反应的产生。与野生型小鼠相比，IL-10 缺陷型小鼠产生的 IFN-γ水平显著更高，肺部积累的白细胞数量更多，并且更快地清除了百日咳博德特氏菌。这些数据表明，百日咳博德特氏菌诱导产生了 IL-10，这通过限制保护性 IFN-γ反应来促进其在感染宿主内的持续存在。
