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

• 成果类型: Article
• 署名作者: Catta-Preta, Carolina M. C.; Ghosh, Kashinath; Sacks, David L.; Ferreira, Tiago R.
• 署名单位: National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-15088
• DOI: 10.1073/pnas.2406776121
• 发表日期: 2024-12-24
• 关键词: gene-expression; transmission; stage; vector; differentiation; cycle

摘要

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.