Sekine Hideaki, Taguchi Haruhiko, Watanabe Hidehiro, Kawai Shin, Fujioka Yasunori, Goto Hajime, Kobayashi Hiroyuki, Kamiya Shigeru
Department of First Internal Medicine, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan.
Department of Infectious Diseases, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan.
J Med Microbiol. 2009 Jun;58(Pt 6):697-705. doi: 10.1099/jmm.0.007872-0.
Although mycoplasmal pneumonia has been generally considered to be a disease with good prognosis, a pathogenic host immune response has been associated with its occurrence. In the present study, the pathogenic significance of the immune response was examined using germ-free mice either infected intranasally with Mycoplasma pneumoniae or inoculated with M. pneumoniae antigens (soluble antigen and partially purified antigen). In gnotobiotic mice monoassociated with M. pneumoniae, 10(4) c.f.u. M. pneumoniae per lung were isolated 2-28 days after infection. Inflammatory changes with infiltration of lymphocytes were histopathologically detected in the perivascular area at 2 and 7 days after infection. In the mice intranasally inoculated with soluble antigen or partially purified antigens (F6 and F10 antigens), infiltration of neutrophils and lymphocytes was histopathologically detected at 2 days after inoculation. Severe pneumonia with tissue destruction was observed in the mice inoculated with F6 antigen. A gamma interferon (IFN-gamma) dominant response in endogenous cytokine expression was observed in all the treated mice. These results indicate that inflammatory changes in the lung tissue were prolonged in gnotobiotic mice monoassociated with M. pneumoniae compared with mice inoculated with M. pneumoniae antigen. In addition, it was shown that IFN-gamma plays an important role in the pathogenesis of pneumonia in mice either infected with M. pneumoniae or inoculated with its antigen. In particular, the F6 antigen has been considered to be an important virulence factor in terms of induction of tissue injury causing infiltration of lymphocytes and neutrophils in the lung, suggesting a close interaction between the immune response and the occurrence of M. pneumoniae pneumonia.
虽然支原体肺炎通常被认为是一种预后良好的疾病,但其发病与致病性宿主免疫反应有关。在本研究中,使用无菌小鼠进行实验,这些小鼠要么经鼻感染肺炎支原体,要么接种肺炎支原体抗原(可溶性抗原和部分纯化抗原),以检验免疫反应的致病意义。在与肺炎支原体单联的悉生小鼠中,感染后2 - 28天,每只肺可分离出10⁴ c.f.u.的肺炎支原体。感染后2天和7天,组织病理学检测发现血管周围区域有淋巴细胞浸润的炎症变化。在经鼻接种可溶性抗原或部分纯化抗原(F6和F10抗原)的小鼠中,接种后2天组织病理学检测到中性粒细胞和淋巴细胞浸润。在接种F6抗原的小鼠中观察到伴有组织破坏的严重肺炎。在所有处理过的小鼠中均观察到内源性细胞因子表达以γ干扰素(IFN - γ)为主的反应。这些结果表明,与接种肺炎支原体抗原的小鼠相比,与肺炎支原体单联的悉生小鼠肺组织中的炎症变化持续时间更长。此外,研究表明IFN - γ在感染肺炎支原体或接种其抗原的小鼠肺炎发病机制中起重要作用。特别是,就诱导导致肺内淋巴细胞和中性粒细胞浸润的组织损伤而言,F6抗原被认为是一种重要的毒力因子,这表明免疫反应与肺炎支原体肺炎发病之间存在密切相互作用。