TY - JOUR
T1 - Regulation of midgut cell proliferation impacts Aedes aegypti susceptibility to dengue virus
AU - Taracena, Mabel L.
AU - Bottino-Rojas, Vanessa
AU - Talyuli, Octavio A.C.
AU - Walter-Nuno, Ana Beatriz
AU - Oliveira, José Henrique M.
AU - Angleró-Rodriguez, Yesseinia I.
AU - Wells, Michael B.
AU - Dimopoulos, George
AU - Oliveira, Pedro L.
AU - Paiva-Silva, Gabriela O.
N1 - Funding Information:
This work was supported by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (INCT_EM, 16/2014) to GOPS and PLO, Fundação Carlos Chagas Filho de Amparo à Pesquisa de Estado do Rio de Janeiro (FAPERJ)(26/010.001545/2014) and by National Institutes of Health, National Institute for Allergy and Infectious Disease, R01AI101431 to GD. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank all members of the Laboratory of Biochemistry of Hematophagous Arthropods, especially Jaciara Loredo, Mônica Sales and S.R. Cassia for providing technical assistance. We also thank Dr. Helena Araujo (ICB, UFRJ) for all the technical advice and assistance with the microscopy experiments. We would like to thank the Johns Hopkins Malaria Research Institute Insectary.
Publisher Copyright:
© 2018 Taracena et al. http://creativecommons.org/licenses/by/4.0/
PY - 2018/5/21
Y1 - 2018/5/21
N2 - Aedes aegypti is the vector of some of the most important vector-borne diseases like dengue, chikungunya, zika and yellow fever, affecting millions of people worldwide. The cellular processes that follow a blood meal in the mosquito midgut are directly associated with pathogen transmission. We studied the homeostatic response of the midgut against oxidative stress, as well as bacterial and dengue virus (DENV) infections, focusing on the proliferative ability of the intestinal stem cells (ISC). Inhibition of the peritrophic matrix (PM) formation led to an increase in reactive oxygen species (ROS) production by the epithelial cells in response to contact with the resident microbiota, suggesting that maintenance of low levels of ROS in the intestinal lumen is key to keep ISCs division in balance. We show that dengue virus infection induces midgut cell division in both DENV susceptible (Rockefeller) and refractory (Orlando) mosquito strains. However, the susceptible strain delays the activation of the regeneration process compared with the refractory strain. Impairment of the Delta/Notch signaling, by silencing the Notch ligand Delta using RNAi, significantly increased the susceptibility of the refractory strains to DENV infection of the midgut. We propose that this cell replenishment is essential to control viral infection in the mosquito. Our study demonstrates that the intestinal epithelium of the blood fed mosquito is able to respond and defend against different challenges, including virus infection. In addition, we provide unprecedented evidence that the activation of a cellular regenerative program in the midgut is important for the determination of the mosquito vectorial competence.
AB - Aedes aegypti is the vector of some of the most important vector-borne diseases like dengue, chikungunya, zika and yellow fever, affecting millions of people worldwide. The cellular processes that follow a blood meal in the mosquito midgut are directly associated with pathogen transmission. We studied the homeostatic response of the midgut against oxidative stress, as well as bacterial and dengue virus (DENV) infections, focusing on the proliferative ability of the intestinal stem cells (ISC). Inhibition of the peritrophic matrix (PM) formation led to an increase in reactive oxygen species (ROS) production by the epithelial cells in response to contact with the resident microbiota, suggesting that maintenance of low levels of ROS in the intestinal lumen is key to keep ISCs division in balance. We show that dengue virus infection induces midgut cell division in both DENV susceptible (Rockefeller) and refractory (Orlando) mosquito strains. However, the susceptible strain delays the activation of the regeneration process compared with the refractory strain. Impairment of the Delta/Notch signaling, by silencing the Notch ligand Delta using RNAi, significantly increased the susceptibility of the refractory strains to DENV infection of the midgut. We propose that this cell replenishment is essential to control viral infection in the mosquito. Our study demonstrates that the intestinal epithelium of the blood fed mosquito is able to respond and defend against different challenges, including virus infection. In addition, we provide unprecedented evidence that the activation of a cellular regenerative program in the midgut is important for the determination of the mosquito vectorial competence.
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U2 - 10.1371/journal.pntd.0006498
DO - 10.1371/journal.pntd.0006498
M3 - Article
C2 - 29782512
AN - SCOPUS:85047895338
SN - 1935-2727
VL - 12
JO - PLoS neglected tropical diseases
JF - PLoS neglected tropical diseases
IS - 5
M1 - e0006498
ER -