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以先天免疫系统为目标来治疗肺结核

摘要 : 美国各地以及巴西、中国和印度等国的实验室合作,定义1型干扰素、白介素-1和前列腺素E2这三个免疫调节分子间的相互作用,研究出了一个免疫治疗方法。这项工作是对以寄主“类二十烷酸”网络为目标的治疗方法的一个概念证明,同时也为传统化疗提供了可行的替代方案。相关文章发表于2014年6月25日的《Nature》杂志上。

继能抵抗多种药物的结核分枝杆菌的传播以及由HIV的流行所造成的并发症出现之后,肺结核正在重新成为对公共卫生的一大威胁,而目前仍没有在全球范围内都有效的疫苗。

现在,美国各地以及巴西、中国和印度等国的实验室之间所进行的一项合作研究项目,研究出了一个免疫治疗方法,它通过对细胞因子干扰素(在活动性肺结核中过量存在)和白介素-1(被认为有保护作用)的操纵来针对一个小鼠肺结核模型中的先天免疫系统进行治疗。

Katrin Mayer-Barber及同事发现,这些细胞因子是在功能上通过“类二十烷酸”相联系的。这项工作是对以寄主“类二十烷酸”网络为目标的治疗方法的一个概念证明,同时也为传统化疗提供了可行的替代方案。

原文摘要:

Host-directed therapy of tuberculosis based on interleukin-1 and type I interferon crosstalk

Katrin D. Mayer-Barber, Bruno B. Andrade, Sandra D. Oland, Eduardo P. Amaral, Daniel L. Barber, Jacqueline Gonzales, Steven C. Derrick, Ruiru Shi, Nathella Pavan Kumar, Wang Wei, Xing Yuan, Guolong Zhang, Ying Cai, Subash Babu, Marta Catalfamo, Andres M. Salazar, Laura E. Via, Clifton E. Barry III & Alan Sher

Tuberculosis remains second only to HIV/AIDS as the leading cause of mortality worldwide due to a single infectious agent. Despite chemotherapy, the global tuberculosis epidemic has intensified because of HIV co-infection, the lack of an effective vaccine and the emergence of multi-drug-resistant bacteria. Alternative host-directed strategies could be exploited to improve treatment efficacy and outcome, contain drug-resistant strains and reduce disease severity and mortality. The innate inflammatory response elicited by Mycobacterium tuberculosis (Mtb) represents a logical host target. Here we demonstrate that interleukin-1 (IL-1) confers host resistance through the induction of eicosanoids that limit excessive type I interferon (IFN) production and foster bacterial containment. We further show that, in infected mice and patients, reduced IL-1 responses and/or excessive type I IFN induction are linked to an eicosanoid imbalance associated with disease exacerbation. Host-directed immunotherapy with clinically approved drugs that augment prostaglandin E2 levels in these settings prevented acute mortality of Mtb-infected mice. Thus, IL-1 and type I IFNs represent two major counter-regulatory classes of inflammatory cytokines that control the outcome of Mtb infection and are functionally linked via eicosanoids. Our findings establish proof of concept for host-directed treatment strategies that manipulate the host eicosanoid network and represent feasible alternatives to conventional chemotherapy.

对应Nature杂志: 2014年7月3日Nature杂志精选

来源: Nature中文 浏览次数:76

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