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

crossref(2024)

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摘要
Abstract Leishmania development in the sandfly vector is predominantly characterized as a series of sequential promastigote morphotypes. Apart from isolated mammal-infective metacyclic promastigotes, the transcriptional programs and molecular markers for other stages co-inhabiting the midgut or co-egested by the sandfly have not been resolved. Here, using single-cell RNA-sequencing, we elucidate the transcriptomic complexity of L. major promastigotes colonizing Phlebotomus duboscqi at early- and late-infection, providing unique markers for three subpopulations found in sandflies with mature, transmissible infections. Contrary to prevailing models, our analyses indicate a non-linear developmental program, with bifurcation into either replicating early metacyclics or attached and detached haptomonads. Haptomonads constitute part of the transmitted dose, and along with highly motile, non-dividing late metacyclics, are infectious to and exacerbate the pathology in mice. Our single-cell analysis and novel validated markers will facilitate further studies on the Leishmania life cycle and its implications for host infections.
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