The tripartite interactions between the mosquito, its microbiota and Plasmodium

Abstract

The microbiota of Anopheles mosquitoes interferes with mosquito infection by Plasmodium and influences mosquito fitness, therefore affecting vectorial capacity. This natural barrier to malaria transmission has been regarded with growing interest in the last 20 years, as it may be a source of new transmission-blocking strategies. The last decade has seen tremendous progress in the functional characterisation of the tripartite interactions between the mosquito, its microbiota and Plasmodium parasites. In this review, we provide insights into the effects of the mosquito microbiota on Plasmodium infection and on mosquito physiology, and on how these aspects together influence vectorial capacity. We also discuss three current challenges in the field, namely the need for a more relevant microbiota composition in experimental mosquitoes involved in vector biology studies, for a better characterisation of the non-bacterial microbiota, and for further functional studies of the microbiota present outside the gut.

Keywords: Anopheles; Colonisation resistance; Experimental models; Microbiota; Plasmodium; Vectorial transmission.

Fig. 1

Interactions between the microbiota and Plasmodium in the mosquito midgut. The microbiota affects Plasmodium infection by several mechanisms: (i) Direct impact on parasites via inhibition of its oxidative defence system [13, 20] or by production of uncharacterised antimicrobials [16, 22]. (ii) Stimulation of the NF-κB dependent Immune-deficiency (Imd) pathway, which is regulated by Peptidoglycan Recognition Proteins (PGRPs) and restrains parasite infection [15, 30]. The mechanisms of action of the Imd pathway on parasites are still unclear, they probably include TEP1-dependent and independent components [5, 18, 19]. (iii) Blood meal inducible physical barriers affect gut microbes: a dityrosine network reduces the diffusion of elicitors, thus protecting the microbiota and Plasmodium from immune activation [32] and the microbiota-dependent induction of the peritrophic matrix [24] may have positive and/or negative impacts on parasite infection. Reciprocally, Plasmodium infection inhibits antioxidant enzymes in the mosquito gut, which has been suggested to help parasite infection via a reduction of the mosquito microbiota [21]

Fig. 2

The microbiota impacts several parameters of the Ross-MacDonald model of vectorial transmission. R₀ represents the basic reproductive number, the number of individuals that are expected to get infected via mosquito transmission when a single infected individual is present in a susceptible population. The variables indicated in bold are known to be microbiota-dependent. In grey, the specific effects of the microbiota on mosquito physiology and immunity are specified [, –17, 20, 22, 23, 30, 35]. Potential roles of the mosquito microbiota on biting rate, anthropophily, incubation period and probability of human infection have not yet been investigated

Fig. 3

Alternative models for the study of the mosquito and its microbiota. Besides laboratory conventionally-reared mosquitoes and field-collected mosquitoes, several other microbiota set ups are or may be used to study the mosquito biology. Field bacterial isolates may be used to obtain gnotobiotic mosquitoes, i.e. mosquitoes colonised by known strains of bacteria. Laboratory larvae may be reared in water collected from natural breeding sites, or a first generation of mosquitoes (F1) may be obtained from field collected individuals. Finally, adult mosquitoes may be raised in the laboratory from field collected larvae. None of these models is perfect but each may be more appropriate depending on the aims and requirements of each study. Combining several models may also strengthen experimental work and participate in increasing the reproducibility of results between laboratories