A motogenic GABAergic system of mononuclear phagocytes facilitates dissemination of coccidian parasites.
A motogenic GABAergic system of mononuclear phagocytes facilitates dissemination of coccidian parasites.
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DOI：
10.7554/elife.60528
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发表时间：
2020-11-12
期刊：
影响因子：
7.7
通讯作者：
Barragan A
中科院分区：
文献类型：
--
作者：
Bhandage AK;Olivera GC;Kanatani S;Thompson E;Loré K;Varas-Godoy M;Barragan A
γ-氨基丁酸（GABA）在原核生物和真核生物中具有多种生物学功能，包括脊椎动物的神经传递。然而，GABA在免疫系统中的作用仍然难以捉摸。在此，对人和鼠骨髓单核吞噬细胞的全面表征揭示了存在保守且严格调控的GABA能机制，其表达GABA代谢酶和转运蛋白、GABA-A受体和调节剂以及电压依赖性钙通道。用常见的球虫寄生虫弓形虫和犬新孢子虫感染激发吞噬细胞中的GABA能信号。使用基因沉默和药理学调节剂在体外和体内的小鼠，我们确定的功能决定因素的GABA能信号在寄生的吞噬细胞，并证明了一个链接到钙反应和迁移激活。这些发现揭示了GABA能信号机制在宿主-病原体之间的相互作用中的调节作用。GABA的协同选择是通过特洛伊木马机制在宿主中定植的基础。
Gamma-aminobutyric acid (GABA) serves diverse biological functions in prokaryotes and eukaryotes, including neurotransmission in vertebrates. Yet, the role of GABA in the immune system has remained elusive. Here, a comprehensive characterization of human and murine myeloid mononuclear phagocytes revealed the presence of a conserved and tightly regulated GABAergic machinery with expression of GABA metabolic enzymes and transporters, GABA-A receptors and regulators, and voltage-dependent calcium channels. Infection challenge with the common coccidian parasites Toxoplasma gondii and Neospora caninum activated GABAergic signaling in phagocytes. Using gene silencing and pharmacological modulators in vitro and in vivo in mice, we identify the functional determinants of GABAergic signaling in parasitized phagocytes and demonstrate a link to calcium responses and migratory activation. The findings reveal a regulatory role for a GABAergic signaling machinery in the host-pathogen interplay between phagocytes and invasive coccidian parasites. The co-option of GABA underlies colonization of the host by a Trojan horse mechanism.