Gut Microbes Egested during Bites of Infected Sand Flies Augment Severity of Leishmaniasis via Inflammasome-Derived IL-1β

Publication date: Available online 28 December 2017
Source:Cell Host & Microbe
Author(s): Ranadhir Dey, Amritanshu B. Joshi, Fabiano Oliveira, Lais Pereira, Anderson B. Guimarães-Costa, Tiago D. Serafim, Waldionê de Castro, Iliano V. Coutinho-Abreu, Parna Bhattacharya, Shannon Townsend, Hamide Aslan, Alec Perkins, Subir Karmakar, Nevien Ismail, Morgan Karetnick, Claudio Meneses, Robert Duncan, Hira L. Nakhasi, Jesus G. Valenzuela, Shaden Kamhawi
Leishmania donovani parasites are the cause of visceral leishmaniasis and are transmitted by bites from phlebotomine sand flies. A prominent feature of vector-transmitted Leishmania is the persistence of neutrophils at bite sites, where they protect captured parasites, leading to enhanced disease. Here, we demonstrate that gut microbes from the sand fly are egested into host skin alongside Leishmania parasites. The egested microbes trigger the inflammasome, leading to a rapid production of interleukin-1β (IL-1β), which sustains neutrophil infiltration. Reducing midgut microbiota by pretreatment of Leishmania-infected sand flies with antibiotics or neutralizing the effect of IL-1β in bitten mice abrogates neutrophil recruitment. These early events are associated with impairment of parasite visceralization, indicating that both gut microbiota and IL-1β are important for the establishment of Leishmania infections. Considering that arthropods harbor a rich microbiota, its potential egestion after bites may be a shared mechanism that contributes to severity of vector-borne disease.

Graphical abstract

Teaser

Neutrophils recruited to sand fly bite sites shelter Leishmania, augmenting disease. Dey et al. demonstrate that egestion of sand fly gut microbes into host skin primes the inflammasome to produce IL-1β, which sustains neutrophil recruitment. Removing gut microbiota or blocking IL-1β before transmission abolishes neutrophil recruitment and impairs Leishmania dissemination.


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