Zuñiga Joaquin, Torres-García Diana, Santos-Mendoza Teresa, Rodriguez-Reyna Tatiana S, Granados Julio, Yunis Edmond J
Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, 14080 Mexico City, DF, Mexico.
Clin Dev Immunol. 2012;2012:193923. doi: 10.1155/2012/193923. Epub 2012 May 17.
Mycobacterium tuberculosis (Mtb) infection is a major international public health problem. One-third of the world's population is thought to have latent tuberculosis, a condition where individuals are infected by the intracellular bacteria without active disease but are at risk for reactivation, if their immune system fails. Here, we discuss the role of nonspecific inflammatory responses mediated by cytokines and chemokines induced by interaction of innate receptors expressed in macrophages and dendritic cells (DCs). We also review current information regarding the importance of several cytokines including IL-17/IL-23 in the development of protective cellular and antibody-mediated protective responses against Mtb and their influence in containment of the infection. Finally, in this paper, emphasis is placed on the mechanisms of failure of Mtb control, including the immune dysregulation induced by the treatment with biological drugs in different autoimmune diseases. Further functional studies, focused on the mechanisms involved in the early host-Mtb interactions and the interplay between host innate and acquired immunity against Mtb, may be helpful to improve the understanding of protective responses in the lung and in the development of novel therapeutic and prophylactic tools in TB.
结核分枝杆菌(Mtb)感染是一个重大的国际公共卫生问题。据认为,全球三分之一的人口患有潜伏性结核病,即个体感染了这种胞内细菌但无活动性疾病,但如果其免疫系统功能衰退,就有重新激活疾病的风险。在此,我们讨论由巨噬细胞和树突状细胞(DC)中表达的固有受体相互作用诱导的细胞因子和趋化因子介导的非特异性炎症反应的作用。我们还综述了当前有关几种细胞因子(包括IL-17/IL-23)在针对Mtb的保护性细胞和抗体介导的保护性反应发展中的重要性及其在感染控制中的影响的信息。最后,本文重点关注Mtb控制失败的机制,包括不同自身免疫性疾病中生物药物治疗诱导的免疫失调。进一步聚焦于早期宿主与Mtb相互作用机制以及宿主固有免疫和获得性免疫针对Mtb相互作用的功能研究,可能有助于增进对肺部保护性反应的理解以及开发结核病新的治疗和预防工具。