Conserved across all animal species, the initial cellular or humoral responses to pathogen challenge are mediated by highly conserved components of the innate immune system. While several key pathways, signaling components, and immune modulators have been described in great detail across taxa, several fundamental questions remain regarding innate immune regulation and activation. As key regulators of immune homeostasis and inflammation, bioactive signaling lipids derived from arachidonic acid collectively known as eicosanoids have integral roles in innate immune function from insects to mammals. However, despite the important role of eicosanoids in mediating cellular immune responses such as phagocytosis, encapsulation, and melanization against invading pathogens, our understanding of eicosanoid signaling in insects is limited by the lack of characterized eicosanoid receptors. Preliminary data examining the role of a candidate prostaglandin E2 (PGE2) receptor suggest that eicosanoid (prostaglandin) signaling is critical to insect innate immune responses that limit pathogen survival in the mosquito host. Therefore, the studies outlined in this proposal will characterize the putative PGE2 receptor in Anopheles gambiae (AgPGE2R) to confirm its functional role in prostaglandin signaling (Aim 1) and to examine the influence of AgPGE2R activation on mosquito cellular immune function (Aim 2). This information will provide new data into the conserved mechanisms of eicosanoid signaling to better define the immune mechanisms in which eicosanoids target and destroy pathogens in an invertebrate system.

Public Health Relevance

Innate immunity is a critical determinant of host survival following immune challenge across all plants and animals. Using the mosquito as an unexplored model system, we examine the mechanisms of lipid signaling components known as eicosanoids on insect innate immune function through the functional characterization of a candidate prostaglandin receptor. With presumed conserved function in vertebrates, these studies offer a novel system for comparative immunology, while providing new insights into the mechanisms of insect innate immunity in an invertebrate model system with important relevance to transmission of mosquito-borne disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI144705-02
Application #
9843484
Study Section
Innate Immunity and Inflammation Study Section (III)
Program Officer
Costero-Saint Denis, Adriana
Project Start
2019-01-01
Project End
2020-12-31
Budget Start
2020-01-01
Budget End
2020-12-31
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Iowa State University
Department
Zoology
Type
Earth Sciences/Resources
DUNS #
005309844
City
Ames
State
IA
Country
United States
Zip Code
50011