Leishmaniasis: the act of transmission

• Published in: Trends in parasitology 2021-11, Vol.37 (11), p.976-987
• Main Authors: Serafim, Tiago D., Coutinho-Abreu, Iliano V., Dey, Ranadhir, Kissinger, Ryan, Valenzuela, Jesus G., Oliveira, Fabiano, Kamhawi, Shaden
• Format: Article
• Language: English
• Subjects: Animals; Disease Vectors; Gastrointestinal Microbiome; gut microbiota; inflammation; Leishmania - physiology; Leishmania transmission; Leishmaniasis; Psychodidae - parasitology; retroleptomonad promastigotes; salivary chemoattractant; sand fly bite
• ISSN: 1471-4922; 1471-5007
• DOI: 10.1016/j.pt.2021.07.003

The contribution of vector transmission to pathogen establishment is largely underrated. For Leishmania, transmission by sand flies is critical to early survival involving an irreproducible myriad of parasite, vector, and host molecules acting in concert to promote infection at the bite site. Here, we review recent breakthroughs that provide consequential insights into how vector transmission of Leishmania unfolds. We focus on recent work pertaining to the effect of gut microbiota, sand fly immunity, and changes in metacyclogenesis upon multiple blood meals, on Leishmania development and transmission. We also explore how sand fly saliva, egested parasite molecules and vector gut microbiota, and bleeding have been implicated in modulating the early innate host response to Leishmania, affecting the phenotype of neutrophils and monocytes arriving at the bite site. The feeding behavior of sand flies is intimately connected to vector competence and success of Leishmania transmission. In the sand fly, a postinfected blood meal prevents loss of parasites and promotes transmissible infections. More blood meals increase sand fly infectiousness through retroleptomonad parasites. In addition, prolonged host bleeding induces heme oxygenase-1 (HO-1) in macrophages, which dampens inflammation and promotes disease tolerance.Sand fly gut microbiota is critical to Leishmania development and promotes transmission through host inflammasome-mediated interleukin (IL)-1β that amplifies neutrophil recruitment.Sand fly yellow proteins in saliva are bona fide neutrophil chemoattractants that promote infection.Neutrophils are central to acute inflammation caused by bite-specific mediators, but dermal resident macrophages are gaining attention as participants that harbor Leishmania parasites early in infection.