Investigation of the impact of the mosquito immune system on shaping the transmitted malaria parasite populations

The Anopheles gambiae immune system forms a barrier to infection of the malaria parasite Plasmodium. Soon after entering the mosquito via a blood meal, parasites are attacked by an array of immune responses that greatly impact on their population size. In nature, only a handful of parasites survive these responses to establish infection. Prior to ookinete traversal of the mosquito midgut epithelium, the antibacterial Imd pathway significantly reduces the number of parasites. However, most losses are recorded after ookinetes traverse the midgut epithelium and encounter the complement-like response. We recently identified several genes that appear to be important for parasite protection from this response. Disruption of any of these genes leads to a variable number of ookinetes that traverse the mosquito midgut epithelium but are eliminated by complement reactions upon reaching the basal sub-epithelial space. Silencing key components of the complement-like system restores parasite development and transmission to a new host. These results led us hypothesise that either all of these genes have essential functions in parasite immune evasion or that loss-of-function of any of them bears a fitness cost exceeding a certain threshold required for parasites to endure the mosquito immune response. With the latter hypothesis, the mosquito immune system acts as a purifying selection filter for parasite populations permitting only the fittest parasites to survive and be transmitted to a new host. This project will further investigate this hypothesis by: (1) examining how the mosquito immune system shapes the parasite populations transmitted between hosts, (2) investigating the impact these responses may have on parasite populations transmitted by different vectors, and (3) characterising the function of prioritised parasite genes and proteins found to play important roles in mosquito infection and examining their potential as targets of transmission blocking interventions.

Project details

Enabling Technologies & Assays
Genetics and Genomics
Vector Control

Jan 2021 — Dec 2023

$880,998

United Kingdom