果蝇免疫研究进展及其感染分枝杆菌的免疫特征

耐药性、持续感染以及与HIV病毒的共感染等诸多因素导致一度得到控制的结核病死灰复燃, 有效控制日益严峻的结核病迫切需要深入认识其致病菌——结核分枝杆菌Mycobacterium tuberculosis的基础生物学特性, 以及宿主相应的免疫控制机理。目前尚无一个动物模型能够同时回答这些关键问题, 而利用多种动物模型有望从不同角度回答上述问题, 普遍认为果蝇Drosophila 是比较理想的研究结核病天然免疫的简易模式动物之一。本文综述了果蝇免疫研究的最新进展, 包括免疫途径及其新成员与负调控子, 重点总结了用海分枝菌杆菌M. marinum、偶发分枝杆菌M. fortuitum和耻垢分枝杆菌M. smegmatis等分枝杆菌感染果蝇的新发现, 其中包括感染期间不诱导抗菌肽表达, 多个宿主因子(如CD36家族成员和ESCRT)参与了应答, 鉴定出具有杀灭分支杆菌作用的β-己糖酰胺酶, 感染期间能量代谢相关基因差异表达等。这些工作为利用果蝇模型快速筛选治疗结核病的新药物靶标和药物先导物提供了思路。

Immune research progress in Drosophila with emphasis on their immune characteristics infected by Mycobacterium

Tuberculosis reestablishes as a predominant threat to human beings. Several factors including multidrug resistance, persistence and co-infection with HIV contributed to its rampancy. More sophisticated understanding of the basic biology of its pathogen, Mycobacterium tuberculosis and the immune response of human beings will be the cornerstone of tuberculosis control and eradication. No single animal model can fully address the magnitudes of its pathogenesis. Integrating knowledge from diverse animal models can be insightful. Drosophila is ideal to address the innate immune response to tuberculosis. Immune response pathway, components of immune response pathway and related negative regulatory factors in Drosophila were reviewed. The major findings employing Mycobacterium infection, especially M. marinum, M. fortuitum and M.smegmatis to challenge Drosophila were summarized. Copious studies demonstrated that no antimicrobial peptides were significantly induced, and multiple host factors such as CD36 family member and ESCRT were involved in the host response. Beta-hexosaminidase related to killing Mycobacterium was identified. Energy metabolism related genes were differentially regulated during infection. These might be helpful to the identification of novel anti-tuberculosis drug targets and lead discovery via the facile Drosophila model.