Atayde Vanessa Diniz, Aslan Hamide, Townsend Shannon, Hassani Kasra, Kamhawi Shaden, Olivier Martin
Department of Medicine, Microbiology and Immunology, McGill University, 3775 University Street, Montréal, QC H3A 2B4, Canada; Infectious Diseases and Immunity in Global Heath Program, Research Institute of the McGill University Health Centre, 1001 Boulevard Décarie, Montréal, QC H4A 3J1, Canada.
Vector Molecular Biology Section, NIH, 12735 Twinbrook Parkway, Rockville, MD 20878, USA; Faculty of Health Science, Selahaddin Eyyubi University, 215 Ba?c?lar Mah. ?anl?urfa Blv Otogar Kar??s?, Diyarbakir, 21090 Ba?lar, Turkey.
Cell Rep. 2015 Nov 3;13(5):957-67. doi: 10.1016/j.celrep.2015.09.058. Epub 2015 Oct 22.
Despite several studies describing the secretion of exosomes by Leishmania in vitro, observation of their formation and release in vivo has remained a major challenge. Herein, we show that Leishmania constitutively secretes exosomes within the lumen of the sand fly midgut through a mechanism homologous to the mammalian pathway. Through egestion experiments, we demonstrate that Leishmania exosomes are part of the sand fly inoculum and are co-egested with the parasite during the insect's bite, possibly influencing the host infectious process. Indeed, co-inoculation of mice footpads with L. major plus midgut-isolated or in-vitro-isolated L. major exosomes resulted in a significant increase in footpad swelling. Notably, co-injections produced exacerbated lesions through overinduction of inflammatory cytokines, in particular IL-17a. Our data indicate that Leishmania exosomes are an integral part of the parasite's infectious life cycle, and we propose to add these vesicles to the repertoire of virulence factors associated with vector-transmitted infections.
尽管有多项研究描述了利什曼原虫在体外分泌外泌体的情况，但在体内观察其形成和释放仍然是一项重大挑战。在此，我们表明利什曼原虫通过一种与哺乳动物途径同源的机制，在白蛉中肠腔内持续分泌外泌体。通过排粪实验，我们证明利什曼原虫外泌体是白蛉接种物的一部分，并且在昆虫叮咬期间与寄生虫一起被排出，这可能会影响宿主的感染过程。事实上，将硕大利什曼原虫与从中肠分离或体外分离的硕大利什曼原虫外泌体共同接种到小鼠足垫中，导致足垫肿胀显著增加。值得注意的是，共同注射通过过度诱导炎性细胞因子，特别是IL-17a，产生了加剧的病变。我们的数据表明，利什曼原虫外泌体是寄生虫感染生命周期的一个组成部分，并且我们建议将这些囊泡添加到与媒介传播感染相关的毒力因子库中。
