Kanaly S T, Hines S A, Palmer G H
Department of Veterinary Microbiology and Pathology, Washington State University, Pullman 99164-7040, USA.
Infect Immun. 1995 Aug;63(8):3037-41. doi: 10.1128/iai.63.8.3037-3041.1995.
Rhodococcus equi, a facultative intracellular bacterium, causes chronic, often fatal granulomatous pneumonia in young horses and in humans with AIDS. The inability of host alveolar macrophages to kill intracellular R. equi results in the development of granulomas and progressive loss of pulmonary parenchyma. Clearance of the organism from the lung requires functional CD4+ T cells. The purpose of this study was to identify the cytokine effector mechanisms that mediate clearance of R. equi from the lung. Mice were treated with monoclonal antibodies (MAbs) to either gamma interferon (IFN-gamma) or interleukin-4 (IL-4) to determine the role of endogenous production of these cytokines in pulmonary clearance of R. equi. Mice treated with an anti-IL-4 or isotype control MAb cleared R. equi by 21 days postinfection and expressed increased levels of IFN-gamma mRNA, as detected by transcriptional analysis of bronchial lymph node CD4+ T cells. In contrast, mice treated with the anti-IFN-gamma MAb failed to express detectable IFN-gamma mRNA, expressed increased levels of IL-4 mRNA, failed to clear pulmonary infection, and developed pulmonary granulomas with large numbers of eosinophils. The enhancement of IL-4 mRNA expression and a predominance of eosinophils in pulmonary lesions of anti-IFN-gamma-treated mice suggest that a nonprotective Th2 response in involved in disease pathogenesis. The association of increased bronchial lymph node CD4+ T-cell IFN-gamma mRNA expression with pulmonary clearance of R. equi suggests that a Th1 response is protective.
马红球菌是一种兼性胞内细菌，可导致幼马和艾滋病患者发生慢性、通常致命的肉芽肿性肺炎。宿主肺泡巨噬细胞无法杀死胞内的马红球菌，导致肉芽肿形成和肺实质的逐渐丧失。从肺部清除该病原体需要功能性CD4+T细胞。本研究的目的是确定介导从肺部清除马红球菌的细胞因子效应机制。用抗γ干扰素（IFN-γ）或白细胞介素-4（IL-4）的单克隆抗体（MAb）处理小鼠，以确定这些细胞因子的内源性产生在马红球菌肺部清除中的作用。用抗IL-4或同型对照单克隆抗体处理的小鼠在感染后21天清除了马红球菌，并通过支气管淋巴结CD4+T细胞的转录分析检测到IFN-γmRNA水平升高。相比之下，用抗IFN-γ单克隆抗体处理的小鼠未能表达可检测到的IFN-γmRNA，IL-4mRNA水平升高，未能清除肺部感染，并形成了含有大量嗜酸性粒细胞的肺肉芽肿。抗IFN-γ处理的小鼠肺部病变中IL-4mRNA表达增强和嗜酸性粒细胞占优势，表明非保护性Th2反应参与了疾病发病机制。支气管淋巴结CD4+T细胞IFN-γmRNA表达增加与马红球菌肺部清除相关，表明Th1反应具有保护作用。
