What impact does the sandfly nanobiome have on leishmaniasis development?

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Leishmaniasis, a complex pattern of diseases caused by sandfly-transmitted Leishmania sp. is responsible for 2 million new infections and 30,000 deaths each year [1]. More than 300 million people live in Leishmania-endemic areas [2]. Infected individuals either succumb to visceral leishmaniasis, if left untreated, or develop disfiguring cutaneous leishmaniasis depending on the Leishmania species involved. In mammals, Leishmania parasites establish persistent infection by inducing macrophage dysfunction through direct manipulation of macrophage signaling.

For almost 25 years we have been deciphering the mechanisms whereby Leishmania exploits macrophage signaling pathways to block microbicidal functions and control innate inflammatory responses during infection [3, 4]. This condition, which concurs to promote dysfunctions by abrogating the ability to mount an effective immune response, favours persistent infection. We further established that Leishmania major surface zinc-metalloprotease GP63 manipulates macrophage responses to promote infection through direct activation of protein tyrosine phosphatases (PTPs) [5], negatively downregulating JAK and MAP kinase pathways, and the cleavage of key signalling molecules such as the transcription factors AP-1 and NF-kB [6–8].

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