Kieffer Tara L, Cowley Siobhan, Nano Francis E, Elkins Karen L
Laboratory of Mycobacterial Diseases and Cellular Immunity, Division of Bacterial and Parasitic Products, CBER/FDA, 1401 Rockville Pike, HFM 431, Bethesda, Rockville, MD 20852, USA.
Microbes Infect. 2003 Apr;5(5):397-403. doi: 10.1016/s1286-4579(03)00052-2.
To further understand the role of LPS in the pathogenesis of Francisella infection, we characterized murine infection with F. novicida, and compared immunobiological activities of F. novicida LPS and the LPS from F. tularensis live vaccine strain (LVS). F. novicida had a lower intradermal LD(50) in BALB/cByJ mice than F. tularensis LVS, and mice given a lethal F. novicida dose intraperitoneally died faster than those given the same lethal F. tularensis LVS dose. However, the pattern of in vivo dissemination was similar, and in vitro growth of both bacteria in bone marrow-derived macrophages was comparable. F. novicida LPS stimulated very modest in vitro proliferation of mouse splenocytes at high doses, but F. tularensis LVS LPS did not. Murine bone marrow macrophages treated in vitro with F. novicida LPS produced IL12 and TNF-alpha, but did not produce detectable interferon-gamma, IL10, or nitric oxide; in contrast, murine macrophages treated with F. tularensis LVS LPS produced none of these mediators. In contrast to clear differences in stimulation of proliferation and especially cytokines, both types of purified LPS stimulated early protection against lethal challenge of mice with F. tularensis LVS, but not against lethal challenge with F. novicida. Thus, although LPS recognition may not be a major factor in engendering protection, the ability of F. novicida LPS to stimulate the production of proinflammatory cytokines including TNF-alpha likely contributes to the increased virulence for mice of F. novicida compared to F. tularensis LVS.
为了进一步了解脂多糖（LPS）在土拉弗朗西斯菌感染发病机制中的作用，我们对新凶手弗朗西斯菌感染小鼠的情况进行了特征描述，并比较了新凶手弗朗西斯菌LPS与土拉热弗朗西斯菌活疫苗株（LVS）LPS的免疫生物学活性。新凶手弗朗西斯菌在BALB/cByJ小鼠中的皮内半数致死剂量（LD50）低于土拉热弗朗西斯菌LVS，腹腔注射致死剂量新凶手弗朗西斯菌的小鼠比注射相同致死剂量土拉热弗朗西斯菌LVS的小鼠死亡更快。然而，体内传播模式相似，两种细菌在骨髓来源巨噬细胞中的体外生长情况相当。高剂量时，新凶手弗朗西斯菌LPS在体外仅能非常微弱地刺激小鼠脾细胞增殖，而土拉热弗朗西斯菌LVS LPS则不能。体外经新凶手弗朗西斯菌LPS处理的小鼠骨髓巨噬细胞可产生白细胞介素12（IL12）和肿瘤坏死因子-α（TNF-α），但未产生可检测到的干扰素-γ、白细胞介素10或一氧化氮；相比之下，经土拉热弗朗西斯菌LVS LPS处理的小鼠巨噬细胞则不产生这些介质。与增殖刺激尤其是细胞因子方面的明显差异相反，两种纯化的LPS均能刺激小鼠对土拉热弗朗西斯菌LVS致死攻击产生早期保护作用，但对新凶手弗朗西斯菌致死攻击则无此作用。因此，尽管LPS识别可能不是产生保护作用的主要因素，但新凶手弗朗西斯菌LPS刺激包括TNF-α在内的促炎细胞因子产生的能力，可能导致新凶手弗朗西斯菌相对于土拉热弗朗西斯菌LVS对小鼠的毒力增强。
