AUTHOR=Bombaça Ana Cristina S. , Gandara Ana Caroline P. , Ennes-Vidal Vitor , Bottino-Rojas Vanessa , Dias Felipe A. , Farnesi Luana C. , Sorgine Marcos H. , Bahia Ana Cristina , Bruno Rafaela V. , Menna-Barreto Rubem F. S. 

TITLE=Aedes aegypti Infection With Trypanosomatid Strigomonas culicis Alters Midgut Redox Metabolism and Reduces Mosquito Reproductive Fitness

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.732925

DOI=10.3389/fcimb.2021.732925

ISSN=2235-2988

ABSTRACT=<p><italic>Aedes aegypti</italic> mosquitoes transmit arboviruses of important global health impact, and their intestinal microbiota can influence vector competence by stimulating the innate immune system. Midgut epithelial cells also produce toxic reactive oxygen species (ROS) by dual oxidases (DUOXs) that are essential players in insect immunity. <italic>Strigomonas culicis</italic> is a monoxenous trypanosomatid that naturally inhabits mosquitoes; it hosts an endosymbiotic bacterium that completes essential biosynthetic pathways of the parasite and influences its oxidative metabolism. Our group previously showed that <italic>S. culicis</italic> hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)-resistant (WTR) strain is more infectious to <italic>A. aegypti</italic> mosquitoes than the wild-type (WT) strain. Here, we investigated the influence of both strains on the midgut oxidative environment and the effect of infection on mosquito fitness and immunity. WT stimulated the production of superoxide by mitochondrial metabolism of midgut epithelial cells after 4 days post-infection, while WTR exacerbated H<sub>2</sub>O<sub>2</sub> production mediated by increased DUOX activity and impairment of antioxidant system. The infection with both strains also disrupted the fecundity and fertility of the females, with a greater impact on reproductive fitness of WTR-infected mosquitoes. The presence of these parasites induced specific transcriptional modulation of immune-related genes, such as <italic>attacin</italic> and <italic>defensin A</italic> during WTR infection (11.8- and 6.4-fold, respectively) and <italic>defensin C</italic> in WT infection (7.1-fold). Thus, we propose that <italic>A. aegypti</italic> oxidative response starts in early infection time and does not affect the survival of the H<sub>2</sub>O<sub>2</sub>-resistant strain, which has a more efficient antioxidant system. Our data provide new biological aspects of <italic>A. aegypti</italic>–<italic>S. culicis</italic> relationship that can be used later in alternative vector control strategies.</p>