Anopheles gambiae pathogen susceptibility: the intersection of genetics, immunity and ecology

Abstract

Mosquitoes are the major arthropod vectors of human diseases such as malaria and viral encephalitis. However, each mosquito species does not transmit every pathogen, owing to reasons that include specific evolutionary histories, mosquito immune system structure, and ecology. Even a competent vector species for a pathogen displays a wide range of variation between individuals for pathogen susceptibility, and therefore efficiency of disease transmission. Understanding the molecular and genetic mechanisms that determine heterogeneities in transmission efficiency within a vector species could help elaborate new vector control strategies. This review discusses mechanisms of host-defense in Anopheles gambiae, and sources of genetic and ecological variation in the operation of these protective factors. Comparison is made between functional studies using Plasmodium or fungus, and we call attention to the limitations of generalizing gene phenotypes from experiments done in a single genetically simple colony.

Figure

Synthetic model depicting the intersection of genetics, ecology and immunity on Anopheles gambiae pathogen susceptibility. Upper panel (Genetics): The genetic location of loci that control P. falciparum infection in the natural A. gambiae population are indicated [3][4,5]. Pfin loci control numbers of normal oocysts following an infected blood meal, Pfmel loci control ookinete melanization, and the Plasmodium Resistance Island comprises a cluster of protective loci on chromosome 2L. Middle panel (Ecology): Genetic and functional mechanisms of Plasmodium resistance can only be tested in female mosquitoes, but some of the same host-defense mechanisms or close variants may be deployed against other pathogens in adult male mosquitoes and larvae of both sexes. Males and larvae are subject to distinct microbial repertoires and immune selective pressure, but microbial repertoires common to all forms may shape shared components of immunity. Lower panel (Immune Specificity): Classes of pathogens that are distinguished by mosquito immunity can be hypothesized, based on differential modes of fine specificity mediated by either APL1A (A-class pathogens, including P. falciparum but not rodent malaria), or APL1C (C-class pathogens, including rodent malaria parasite species but not P. falciparum). Functional tests of other pathogens and immune genes will be necessary to fully define the protective spectra of these and other immune genes, and the network of their interactions [Mosquito pictures: CEPIA, Institut Pasteur].