Single-cell atlas of Leishmania development in sandflies reveals the heterogeneity of transmitted parasites and their role in infection

IF 9.4 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Carolina M. C. Catta-Preta, Kashinath Ghosh, David L. Sacks, Tiago R. Ferreira
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引用次数: 0

Abstract

Sandfly vectors transmit Leishmania through egestion of parasites into the host skin. The transmissible dose is shaped by Leishmania development in the sandfly gut, described as a sequential differentiation of promastigote morphotypes. Apart from isolated mammal-infective metacyclic promastigotes, little is known about the transcriptional programs and molecular markers for other stages coinhabiting the midgut in mature infections and cotransmitted by the sandfly bite. Here, we elucidate the single-cell transcriptomic complexity of Leishmania major colonizing its natural vector Phlebotomus duboscqi at early and late infection, providing markers for three transmissible stages. Contrary to prevailing models, our analyses indicate a nonlinear developmental progression, with bifurcation into either replicating early metacyclics or attached and detached haptomonads. We demonstrate that haptomonads constitute a key component of the transmitted inoculum and, along with nondividing late metacyclics, are infectious to and exacerbate the pathology in mice. Our single-cell analysis and validated markers will facilitate further studies on the Leishmania life cycle and its implications for vector-to-host transmission dynamics.
沙蝇载体通过将寄生虫挤出寄主皮肤来传播利什曼病。传播剂量取决于利什曼原虫在沙蝇肠道中的发育过程,这种发育过程被描述为原虫形态的连续分化。除了分离出的可感染哺乳动物的变态原体外,人们对成熟感染和沙蝇叮咬共同传播的共居中肠的其他阶段的转录程序和分子标记知之甚少。在这里,我们阐明了大利什曼原虫在感染早期和晚期定植于其天然载体 Phlebotomus duboscqi 的单细胞转录组的复杂性,为三个可传播阶段提供了标记。与流行的模型相反,我们的分析表明了一个非线性的发展过程,分叉为复制的早期元clics或附着和分离的钩单体。我们证明,吸虫构成了传播接种体的关键组成部分,并与不分裂的晚期元胞一起,感染并加剧了小鼠的病理变化。我们的单细胞分析和有效标记将有助于进一步研究利什曼病的生命周期及其对病媒-宿主传播动态的影响。
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来源期刊
CiteScore
19.00
自引率
0.90%
发文量
3575
审稿时长
2.5 months
期刊介绍: The Proceedings of the National Academy of Sciences (PNAS), a peer-reviewed journal of the National Academy of Sciences (NAS), serves as an authoritative source for high-impact, original research across the biological, physical, and social sciences. With a global scope, the journal welcomes submissions from researchers worldwide, making it an inclusive platform for advancing scientific knowledge.
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