Aedes aegypti Toll pathway is induced through dsRNA sensing in endosomes

Area of Science:

• * Mosquito immunology
• * Molecular biology
• * Arbovirus research

Background:

• * Mosquitoes possess complex immune responses to combat pathogens, including arboviruses.
• * The Toll pathway is crucial for defending against viruses like dengue and Zika, but virus recognition mechanisms remain unclear.
• * Double-stranded RNA (dsRNA) is a key viral intermediate, but its role in activating non-RNAi mosquito immunity is not fully understood.

Purpose of the Study:

• * To investigate the role of viral double-stranded RNA (dsRNA) in activating mosquito immune responses.
• * To identify the mechanisms and receptors involved in dsRNA recognition and subsequent immune pathway activation.
• * To explore the potential of dsRNA analogs for controlling arbovirus infections in mosquitoes.

Main Methods:

• * Treatment of *Aedes aegypti* mosquitoes and Aag2 cells with polyinosinic-polycytidylic acid (poly I:C), a synthetic dsRNA analog.
• * Assessment of DENV infection levels post-treatment.
• * Transcriptomic analysis of Aag2 cells in response to poly I:C.
• * Cellular localization studies of poly I:C and identification of potential dsRNA receptors.

Main Results:

• * Poly I:C treatment significantly reduced DENV infection in *Aedes aegypti* mosquitoes and Aag2 cells.
• * Transcriptomic data suggested activation of the Toll pathway following poly I:C exposure.
• * Poly I:C was observed to translocate to the endosomal compartment in Aag2 cells.
• * The *A. aegypti* Toll 6 receptor was identified as a putative receptor for dsRNA recognition.

Conclusions:

• * Virus-produced dsRNAs are potent activators of mosquito anti-pathogen immune responses.
• * The *A. aegypti* Toll 6 receptor plays a role in recognizing dsRNA and initiating immune signaling.
• * This study elucidates dsRNA's function in activating non-RNAi immune pathways in mosquitoes, offering insights into arbovirus control strategies.