Examination of Toll pathway interactions during innate immune responses in the mosquito Aedes aegypti
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Date
2020-03-31
Authors
Erdelyan, Cassidy Nathan Garry
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Abstract
Like other insects, mosquitoes rely on innate immunity pathways to provide protection from a diversity of pathogens. As vectors of some of our most serious diseases, mosquitoes must protect themselves from viral (e.g. dengue, West Nile virus) or protozoan (e.g. malaria) pathogens they transmit, and they must also defend themselves from opportunistic bacterial and fungal pathogens that they can acquire following accidental breaks or wounds in their cuticle. Among the insect defense mechanisms is the Toll-mediated pathway, which chiefly protects against Gram-positive bacterial and fungal pathogens, but can also induce antiviral defenses.
In this study, responses of the Toll pathway in the mosquito Aedes aegypti to two different pathogens were examined, with the aim to identify the role of some of the components of the extracellular signaling cascade that activates Toll. In the first part of this study, the interaction between one of the mosquito’s extracellular signaling cascade proteins, modular serine protease (modSP), and a protein of West Nile virus, non-structural protein 1 (NS1) was examined. NS1 in vertebrates can interact with complement proteins to down-regulate the immune responses, and in a previous yeast two-hybrid screen, NS1 was observed to interact with modSP. To assess this interaction and a possible immune modulatory function in the mosquito, the proteins were over-expressed in insect cell cultures and antibody-mediated pull-down methods were used to detect interactions. Conflicting results were obtained using two different antibodies, and consequently, the interaction remains unconfirmed.
In the other part of this study, the mosquito’s response to a Gram-positive bacterium Staphylococcus epidermidis was examined using a transcriptomic approach. Over 40 known or predicted immune response genes were up-regulated following the infection. RNA interference (RNAi)-mediated knockdown of a few genes confirmed their involvement in the immune responses, but their precise roles in the signaling pathway will require further examination.
These findings illustrate that RNA sequencing, coupled with RNAi validation techniques, could provide valuable insights into the adaptations and dynamic nature of the immune system in mosquitoes and could also provide new targets for another generation of mosquito control technologies.
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Keywords
mosquito immunity, RNA interference