|BARLETTA-FERREIRA, ANA - National Institutes Of Health (NIH)|
|Rooney, Alejandro - Alex|
Submitted to: PLOS Neglected Tropical Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/6/2018
Publication Date: 4/23/2018
Citation: Ramirez, J.L., Dunlap, C.A., Muturi, E.J., Barletta-Ferreira, A.B., Rooney, A.P. 2018. Entomopathogenic fungal infection leads to temporospatial modulation of the mosquito immune system. PLOS Neglected Tropical Diseases. 12:e0006433. https://doi.org/10.1371/journal.pntd.0006433.
Interpretive Summary: The recent increase in new and re-emerging vector borne diseases highlights the need for alternative methods of mosquito control. Fungal entomopathogens show great promise as potential alternatives to chemical insecticides because of their ecofriendly nature and its ability to infect mosquitoes on contact. Here we characterize the temporospatial interactions between the mosquito Ae. aegypti and several entomopathogenic fungi. Our study shows a contrasting tissue and time-specific differences in immune response that vary according to the fungal entomopathogen. Furthermore, fungal infection leads to drastic changes in phenoloxidase activity and midgut ROS production that in turn leads to midgut dysbiosis. This study provides new insights into mosquito-fungal entomopathogen interaction which could facilitate the development of more effective fungal-based biocontrol strategies.
Technical Abstract: Alternative methods of mosquito control are needed to tackle the rising burden of mosquito-borne diseases while minimizing the use of synthetic insecticides which are not only harmful to the environment but also are increasingly threatened by the rapid and widespread development of insecticide resistance in mosquito populations. Fungal-based biopesticides show great promise as potential alternatives to chemical insecticides because of their ecofriendly nature and its ability to infect mosquitoes on contact. Here we describe the temporospatial interactions between the mosquito Aedes aegypti and several entomopathogenic fungi. Fungal infection assays followed by the molecular assessment of infection-responsive genes revealed an intricate interaction between the fungal entomopathogen and the mosquito immune system. We observed contrasting tissue and time-specific differences in the activation of immune signaling pathways and antimicrobial peptide expression. Enzyme activity-based assays showed decreased phenoloxidase (PO) activity at 3 and 6d post-fungal infection. Moreover, fungal infection led to an increase in midgut microbiota that appeared to be attributed in part to reduced midgut reactive oxygen species (ROS) activity. Illumina-based 16s rRNA sequencing showed no significant differences among treatment groups, suggesting equal increases of bacterial species during fungal infection. However, this increase in microbiota does not appear to affect survival of infected mosquitoes. This study revealed compartment-specific responses that vary according to the fungal entomopathogen and to the time post-infection, and appear to act in concert to limit fungal dissemination. Our study provides new insights into this intricate multipartite interaction which could facilitate the development of novel fungal-based biocontrol strategies.