Blood Meal-Derived Heme Decreases ROS Levels in the Midgut of Aedes aegypti and Allows Proliferation of Intestinal Microbiota

PLoS Pathogens

Rubem F. S. Menna-Barreto¹  Francisco R. M. Laurindo¹  Renata L. S. Gonçalves¹  Mário A. C. Silva-Neto²  Flavio A. Lara³  Ana Caroline P. Gandara⁴  Meredith C. Edwards⁴  Jose Henrique M. Oliveira⁴  Marcos H. F. Sorgine⁴  Felipe A. Dias⁵  Pedro L. Oliveira⁶ 

[1] Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular (INCT-EM), Brasil;Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil;Laboratório de Bioquímica Redox, Instituto de Bioquímica Médica, Programa de Biologia Molecular e Biotecnologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil;Laboratório de Bioquímica de Artrópodes Hematófagos, Instituto de Bioquímica Médica, Programa de Biologia Molecular e Biotecnologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil;Laboratório de Microbiologia Celular, Pavilhão Hanseníase, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil;Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brasil

关键词: Mosquitoes;    Heme;    Blood;    Enterobacter infections;    Aedes aegypti;    Redox signaling;    Gut bacteria;    Bacterial diseases;   

DOI  :  10.1371/journal.ppat.1001320

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The presence of bacteria in the midgut of mosquitoes antagonizes infectious agents, such as Dengue and Plasmodium, acting as a negative factor in the vectorial competence of the mosquito. Therefore, knowledge of the molecular mechanisms involved in the control of midgut microbiota could help in the development of new tools to reduce transmission. We hypothesized that toxic reactive oxygen species (ROS) generated by epithelial cells control bacterial growth in the midgut of Aedes aegypti, the vector of Yellow fever and Dengue viruses. We show that ROS are continuously present in the midgut of sugar-fed (SF) mosquitoes and a blood-meal immediately decreased ROS through a mechanism involving heme-mediated activation of PKC. This event occurred in parallel with an expansion of gut bacteria. Treatment of sugar-fed mosquitoes with increased concentrations of heme led to a dose dependent decrease in ROS levels and a consequent increase in midgut endogenous bacteria. In addition, gene silencing of dual oxidase (Duox) reduced ROS levels and also increased gut flora. Using a model of bacterial oral infection in the gut, we show that the absence of ROS resulted in decreased mosquito resistance to infection, increased midgut epithelial damage, transcriptional modulation of immune-related genes and mortality. As heme is a pro-oxidant molecule released in large amounts upon hemoglobin degradation, oxidative killing of bacteria in the gut would represent a burden to the insect, thereby creating an extra oxidative challenge to the mosquito. We propose that a controlled decrease in ROS levels in the midgut of Aedes aegypti is an adaptation to compensate for the ingestion of heme.

【 授权许可】

CC BY