Mosquito Trilogy: Microbiota, Immunity and Pathogens, and Their Implications for the Control of Disease Transmission

Abstract

In mosquitoes, the interaction between the gut microbiota, the immune system, and the pathogens that these insects transmit to humans and animals is regarded as a key component toward the development of control strategies, aimed at reducing the burden of severe diseases, such as malaria and dengue fever. Indeed, different microorganisms from the mosquito microbiota have been investigated for their ability to affect important traits of the biology of the host insect, related with its survival, development and reproduction. Furthermore, some microorganisms have been shown to modulate the immune response of mosquito females, significantly shaping their vector competence. Here, we will review current knowledge in this field, focusing on i) the complex interaction between the intestinal microbiota and mosquito females defenses, both in the gut and at humoral level; ii) how knowledge on these issues contributes to the development of novel and targeted strategies for the control of mosquito-borne diseases such as the use of paratransgenesis or taking advantage of the relationship between Wolbachia and mosquito hosts. We conclude by providing a brief overview of available knowledge on microbiota-immune system interplay in major insect vectors.

Keywords: Wolbachia; control strategies; insects; pathogens; vector-borne diseases.

FIGURE 1

The interaction between gut immune response, microbiota and pathogens in mosquito females. (A) The strong increase of gut-associated microbial load after blood meal induces the activation of the IMD pathway in midgut epithelial cells and the release of antimicrobial peptides (AMPs). The contact between bacterial cells or bacterial-associated molecules (such as peptidoglycans) and epithelium is partially prevented by the peritrophic matrix (PM) which forms soon after a blood meal. Other mosquito-secreted molecules can be exploited by the bacteria as protection from AMPs, such as C-type lectins. When the PM integrity is impaired (B) by the action, for example, of the Plasmodium ookinetes, the IMD pathway is activated and hemocytes are recruited to the infection site at the base of the epithelium thanks to the release of prostaglandin E2 by midgut cells. Apart from activating vector immune response some bacterial species are able to directly limit (C) or to favor (D) pathogen and virus infection in mosquitoes.

FIGURE 2

Paratransgenesis as a tool for the control of mosquito-borne diseases. (A) Example of application of a paratransgenesis based-approach for the control of mosquito vector competence. Engineered symbionts colonize midgut and reproductive organs of Anopheles gambiae mosquitoes and express anti-pathogen effector molecules, leading to the inhibition of Plasmodium parasite development. (B) Example of application of the Wolbachia based-approach. Wolbachia is artificially introduced into the Aedes aegypti mosquitoes; these bacteria can block development of viruses such as dengue and Zika, through priming the response of the insect immune system or competing for nutrients.