Salmon Didier
Institute of Medical Biochemistry Leopoldo de Meis, Centro de Ciências e da Saúde, Federal University of Rio de Janeiro, Av. Brigadeiro Trompowski, Rio de Janeiro 21941-590, Brazil.
Pathogens. 2018 Apr 25;7(2):48. doi: 10.3390/pathogens7020048.
, etiological agent of Sleeping Sickness in Africa, is the prototype of African trypanosomes, protozoan extracellular flagellate parasites transmitted by saliva (). In these parasites the molecular controls of the cell cycle and environmental sensing are elaborate and concentrated at the flagellum. Genomic analyses suggest that these parasites appear to differ considerably from the host in signaling mechanisms, with the exception of receptor-type adenylate cyclases (AC) that are topologically similar to receptor-type guanylate cyclase (GC) of higher eukaryotes but control a new class of cAMP targets of unknown function, the cAMP response proteins (CARPs), rather than the classical protein kinase A cAMP effector (PKA). possesses a large polymorphic family of ACs, mainly associated with the flagellar membrane, and these are involved in inhibition of the innate immune response of the host prior to the massive release of immunomodulatory factors at the first peak of parasitemia. Recent evidence suggests that in several insect-specific AC isoforms are involved in social motility, whereas only a few AC isoforms are involved in cytokinesis control of bloodstream forms, attesting that a complex signaling pathway is required for environmental sensing. In this review, after a general update on cAMP signaling pathway and the multiple roles of cAMP, I summarize the existing knowledge of the mechanisms by which pathogenic microorganisms modulate cAMP levels to escape immune defense.
布氏锥虫是非洲昏睡病的病原体，是非洲锥虫的原型，是通过唾液传播的原生动物细胞外鞭毛虫寄生虫。在这些寄生虫中，细胞周期和环境感知的分子控制机制复杂且集中在鞭毛上。基因组分析表明，这些寄生虫在信号传导机制上似乎与宿主有很大不同，但受体型腺苷酸环化酶（AC）除外，其拓扑结构与高等真核生物的受体型鸟苷酸环化酶（GC）相似，但控制一类功能未知的新型cAMP靶标，即cAMP反应蛋白（CARP），而不是经典的蛋白激酶A cAMP效应器（PKA）。布氏锥虫拥有一个主要与鞭毛膜相关的大型多态性AC家族，这些AC在寄生虫血症第一个高峰大量释放免疫调节因子之前参与抑制宿主的先天免疫反应。最近的证据表明，在布氏锥虫中，几种昆虫特异性AC同工型参与社会运动，而只有少数AC同工型参与血流形式的胞质分裂控制，这证明环境感知需要复杂的信号通路。在这篇综述中，在对cAMP信号通路和cAMP的多种作用进行了一般性更新之后，我总结了致病微生物调节cAMP水平以逃避免疫防御的机制的现有知识。
