Reactive Oxygen Species-mediated Immunity against Leishmania mexicana and Serratia marcescens in the Phlebotomine Sand Fly Lutzomyia longipalpis

Hector Diaz-Albiter,Mauricio R.V Sant'Anna,Fernando A Genta,Rod J Dillon

doi:10.1074/jbc.m112.376095

Hector Diaz-Albiter, Mauricio R.V Sant'Anna + Show 2 more

Open Access

https://doi.org/10.1074/jbc.m112.376095

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Abstract

Phlebotomine sand flies are the vectors of medically important Leishmania. The Leishmania protozoa reside in the sand fly gut, but the nature of the immune response to the presence of Leishmania is unknown. Reactive oxygen species (ROS) are a major component of insect innate immune pathways regulating gut-microbe homeostasis. Here we show that the concentration of ROS increased in sand fly midguts after they fed on the insect pathogen Serratia marcescens but not after feeding on the Leishmania that uses the sand fly as a vector. Moreover, the Leishmania is sensitive to ROS either by oral administration of ROS to the infected fly or by silencing a gene that expresses a sand fly ROS-scavenging enzyme. Finally, the treatment of sand flies with an exogenous ROS scavenger (uric acid) altered the gut microbial homeostasis, led to an increased commensal gut microbiota, and reduced insect survival after oral infection with S. marcescens. Our study demonstrates a differential response of the sand fly ROS system to gut microbiota, an insect pathogen, and the Leishmania that utilize the sand fly as a vehicle for transmission between mammalian hosts.

Highlights

Reactive oxygen species are part of the sand fly innate immune system
Reactive oxygen species (ROS) Regulatory Gene Sequences from cDNA Libraries Constructed from Whole-body versus Midgut Exhibit High Similarity and Identity—Sequences corresponding to catalase, Cu/Zn superoxide dismutase, and peroxiredoxin retrieved from a sand fly whole body cDNA library showed a high level of identity and similarity against sequences obtained from a midgutspecific library (Table 1) (GenBank ABV60342, ABV60343, and ABV60347) [31], suggesting that these genes are expressed in the midgut of L. longipalpis
Serratia and Not Leishmania Induces Changes in H2O2 Concentration in the Midgut—Catalase degrades toxic H2O2 into water and oxygen. To understand whether these changes in catalase expression have an effect on hydrogen peroxide levels, midgut-specific H2O2 concentration was measured in L. mexicana- and S. marcescens-infected L. longipalpis

Summary

Introduction

Reactive oxygen species are part of the sand fly innate immune system. Results: ROS production in the gut increases in response to a bacterial pathogen but not to Leishmania. Significance: The successful use of sand flies as vehicles for Leishmania transmission relies partially on the parasite circumventing the ROS immune response. Reactive oxygen species (ROS) are a major component of insect innate immune pathways regulating gut-microbe homeostasis. We show that the concentration of ROS increased in sand fly midguts after they fed on the insect pathogen Serratia marcescens but not after feeding on the Leishmania that uses the sand fly as a vector. The treatment of sand flies with an exogenous ROS scavenger (uric acid) altered the gut microbial homeostasis, led to an increased commensal gut microbiota, and reduced insect survival after oral infection with S. marcescens. Our study demonstrates a differential response of the sand fly ROS system to gut microbiota, an insect pathogen, and the Leishmania that utilize the sand fly as a vehicle for transmission between mammalian hosts

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