Rottman Martin, Catherinot Emilie, Hochedez Patrick, Emile Jean-François, Casanova Jean-Laurent, Gaillard Jean-Louis, Soudais Claire
Laboratoire de Microbiologie, Hôpital R. Poincaré, 104 Bd Raymond Poincaré, 92380 Garches, France.
Infect Immun. 2007 Dec;75(12):5898-907. doi: 10.1128/IAI.00014-07. Epub 2007 Sep 17.
Mycobacterium abscessus is an emerging rapidly growing mycobacterium that causes tuberculous-like lesions in humans. We studied the immune control of this organism in C57BL/6 mice challenged intravenously with 10(7) CFU. Bacteria were eliminated from both the spleen and the liver within 90 days, and liver histology showed organized granulomatous lesions. A T- and B-cell requirement was investigated by challenging Rag2-/-, Cd3epsilon-/-, and muMT-/- mice. Rag2-/- and Cd3epsilon-/- mice were significantly impaired in the ability to clear M. abscessus from the liver and spleen, and muMT-/- mice were significantly impaired in the ability to clear M. abscessus from the liver, suggesting that infection control was primarily T cell dependent in the spleen and both T and B cell dependent in the liver. The liver granulomatous response was similar to that of wild-type controls in muMT-/- mice but completely absent in Cd3epsilon-/- and Rag2-/- mice. We studied the involvement of gamma interferon (IFN-gamma) and tumor necrosis factor (TNF) by challenging C57BL/6 mice deficient in the IFN-gamma receptor (Ifngr1-/-) and in TNF (Tnf-/-). Ifngr1-/- mice were significantly impaired in M. abscessus control both in the spleen and in the liver, and granulomas were profoundly altered. The effect was even more substantial in Tnf-/- mice; they failed to control M. abscessus infection in the liver and died within 20 to 25 days after infection with many hepatic inflammatory foci and major lesions of ischemic necrosis in the liver and kidney. These features were not observed with the closely related species M. chelonae. T-cell immunity, IFN-gamma, and TNF are central factors for the control of M. abscessus in C57BL/6 mice, as they are for the control of pathogenic slowly growing mycobacteria.
脓肿分枝杆菌是一种新出现的快速生长分枝杆菌，可在人类中引起结核样病变。我们研究了用10⁷CFU静脉内攻击的C57BL/6小鼠对该菌的免疫控制情况。90天内细菌从脾脏和肝脏中被清除，肝脏组织学显示有组织化的肉芽肿性病变。通过对Rag2⁻/⁻、Cd3ε⁻/⁻和μMT⁻/⁻小鼠进行攻击来研究T细胞和B细胞的需求。Rag2⁻/⁻和Cd3ε⁻/⁻小鼠从肝脏和脾脏清除脓肿分枝杆菌的能力显著受损，而μMT⁻/⁻小鼠从肝脏清除脓肿分枝杆菌的能力显著受损，这表明在脾脏中感染控制主要依赖T细胞，而在肝脏中则依赖T细胞和B细胞。μMT⁻/⁻小鼠肝脏的肉芽肿反应与野生型对照相似，但在Cd3ε⁻/⁻和Rag2⁻/⁻小鼠中则完全没有。我们通过对缺乏γ干扰素（IFN-γ）受体（Ifngr1⁻/⁻）和肿瘤坏死因子（TNF）（Tnf⁻/⁻）的C57BL/6小鼠进行攻击来研究IFN-γ和TNF的参与情况。Ifngr1⁻/⁻小鼠在脾脏和肝脏中对脓肿分枝杆菌的控制均显著受损，肉芽肿也发生了深刻改变。在Tnf⁻/⁻小鼠中这种影响更为显著；它们无法控制肝脏中的脓肿分枝杆菌感染，在感染后20至25天内死亡，肝脏有许多炎症病灶，肝脏和肾脏有严重的缺血性坏死病变。与密切相关的龟分枝杆菌相比，未观察到这些特征。T细胞免疫、IFN-γ和TNF是C57BL/6小鼠控制脓肿分枝杆菌的核心因素，就像它们是控制致病性缓慢生长分枝杆菌的核心因素一样。
