Immune response and insulin signaling enhance malaria transmission

The spread of vector-borne diseases depends on vector behavior that puts infected vectors in contact with susceptible hosts. Propensity of mosquitoes to feed on hosts changes dynamically over the course of malaria infection, with infected mosquitoes more likely to take a bloodmeal during infectious stages of parasite development than during uninfectious stages. Although these behavioral changes have been shown to occur in response to general immune challenges as well, the mechanism causing mosquitoes to change behavior when undergoing immune challenge or malaria infection was unclear. Recent work by Lauren Cator and CIDD colleagues Courtney Murdock, Johanna Ohm, Matt Thomas and Andrew Read, along with Shirley Luckhart, Jose Pietri and Edwin Lewis at University of California, Davis, has demonstrated that although both a general immune challenge and malaria generate the phenotype of altered feeding behavior in mosquitoes, both of these immune challenges need to be coincident with the timing of the mosquito’s bloodmeal for the behavioral change to occur. When behavioral changes did occur, whether by an immune-challenge with active malaria infection or by a general immune response generated with heat-killed bacteria, the researchers found that low expression of two genes associated with insulin signaling was associated with decreased feeding, and both these genes were upregulated when feeding behavior was enhanced. Artificially knocking down these genes recreated the phenotype of reduced feeding propensity.

When researchers explored the consequence of this altered phenotype mediated by gene expression patterns, they found that mosquito lifespans were significantly enhanced by delaying feeding until later days after an immune-challenge. Longer life-spans of mosquitoes that restrict feeding behavior during early days after an immune challenge, translates into more mosquitoes surviving long enough to transmit parasites. Collectively the results published this month in Nature Scientific Reports suggest that altered feeding behavior of mosquitoes during malaria infection extends vector lifespan and these behaviors are mediated by the expression of genes involved in insulin signaling pathways. These new insights may lead to novel vector control interventions and change our understanding of malaria transmission patterns.