Quesniaux Valerie F J, Jacobs Muazzam, Allie Nasiema, Grivennikov Sergei, Nedospasov Sergei A, Garcia Irene, Olleros Maria L, Shebzukhov Yuriy, Kuprash Dmitry, Vasseur Virginie, Rose Stephanie, Court Nathalie, Vacher Rachel, Ryffel Bernhard
Molecular Immunology and Embryology UMR6218, Orleans University and CNRS, Orleans, France.
Curr Dir Autoimmun. 2010;11:157-79. doi: 10.1159/000289204. Epub 2010 Feb 18.
TNF is essential to control Mycobacterium tuberculosis infection and cannot be replaced by other proinflammatory cytokines. Overproduction of TNF may cause immunopathology, while defective TNF production results in uncontrolled infection. The critical role of TNF in the control of tuberculosis has been illustrated recently by primary and reactivation of latent infection in some patients under pharmacological anti-TNF therapy for rheumatoid arthritis or Crohn's disease. In this review, we discuss results of recent studies aimed at better understanding of molecular, cellular and kinetic aspects of TNF-mediated regulation of host-mycobacteria interactions. In particular, recent data using either mutant mice expressing solely membrane TNF or specific inhibitor sparing membrane TNF demonstrated that membrane TNF is sufficient to control acute M. tuberculosis infection. This is opening the way to selective TNF neutralization that might retain the desired anti-inflammatory effect but reduce the infectious risk.
肿瘤坏死因子（TNF）对于控制结核分枝杆菌感染至关重要，且无法被其他促炎细胞因子所替代。TNF的过度产生可能会导致免疫病理学改变，而TNF产生缺陷则会导致感染失控。近期，类风湿关节炎或克罗恩病患者在接受抗TNF药物治疗时出现潜伏感染的原发和再激活，这说明了TNF在控制结核病方面的关键作用。在本综述中，我们讨论了近期研究的结果，这些研究旨在更好地理解TNF介导的宿主与分枝杆菌相互作用的分子、细胞和动力学方面。特别是，最近使用仅表达膜TNF的突变小鼠或保留膜TNF的特异性抑制剂所获得的数据表明，膜TNF足以控制急性结核分枝杆菌感染。这为选择性TNF中和开辟了道路，这种方法可能会保留所需的抗炎作用，但降低感染风险。
