Mosquito-fungus interactions and antifungal immunity

Abstract

The mosquito immune system has evolved in the presence of continuous encounters with fungi that range from food to foes. Herein, we review the field of mosquito-fungal interactions, providing an overview of current knowledge and topics of interest. Mosquitoes encounter fungi in their aquatic and terrestrial habitats. Mosquito larvae are exposed to fungi on plant detritus, within the water column, and at the water surface. Adult mosquitoes are exposed to fungi during indoor and outdoor resting, blood and sugar feeding, mating, and oviposition. Fungi enter the mosquito body through different routes, including ingestion and through active or passive breaches in the cuticle. Oral uptake of fungi can be beneficial to mosquitoes, as yeasts hold nutritional value and support larval development. However, ingestion of or surface contact with fungal entomopathogens leads to colonization of the mosquito with often lethal consequences to the host. The mosquito immune system recognizes fungi and mounts cellular and humoral immune responses in the hemocoel, and possibly epithelial immune responses in the gut. These responses are regulated transcriptionally through multiple signal transduction pathways. Proteolytic protease cascades provide additional regulation of antifungal immunity. Together, these immune responses provide an efficient barrier to fungal infections, which need to be overcome by entomopathogens. Therefore, fungi constitute an excellent tool to examine the molecular underpinnings of mosquito immunity and to identify novel antifungal peptides. In addition, recent advances in mycobiome analyses can now be used to examine the contribution of fungi to various mosquito traits, including vector competence.

Keywords: Entomopathogen; Humoral immunity; Infection; Melanization; Mycobiota.

Figure 1:. The multitude of potential fungus-mosquito encounters.

Adult mosquitoes are exposed to fungi on a multitude of surfaces during indoor and outdoor resting (A, D, H), blood and sugar feeding (C, G). Additional fungal encounters can occur during mating (B) and oviposition (E). Mosquito larvae in their aquatic environment are exposed to fungi on plant detritus, within the water column, and at the water surface (F).

Figure 2:. Entry routes of fungal entomopathogens into their mosquito hosts.

Entomopathogens enter mosquito larvae and adults through two distinct routes. Top panel: Fungal and water mold asexual spores attach to the mosquito cuticle and penetrate actively via penetration pegs. Opportunistic fungal pathogens can gain entry through wound sites. Center panel: Ingested spores may be degraded through digestive enzymes in the larval midgut, resulting in toxin release. Some spores may germinate and penetrate through the midgut epithelium, subseuqently disseminating throughout the larval body. It is unclear, whether this occurs in adult mosquitoes. Bottom panel: Trichospores of Smittium sp. attach to the cuticular lining of the hindgut in mosquito larvae, germinate and grow locally. Hyphae of Smittium morbosum can grow anteriorly, and penetrate the posterior midgut epithelium, where they are melanized.

Figure 3:. Immune modules that regulate mosquito antifungal immunity.

Fungi that penetrate epithelia and reach the hemolymph, as indicated by the germinating blastospore drawing, are attacked by multiple antifungal molecules. These molecules can be expression products of signal transduction pathways, including the Toll, IMD, JAK/STAT and MAPK pathways. Alternatively, these molecules are proteolytic activation products of humoral killing modules, circulating in the hemolymph, including PO and TEP1, which are products of the melanization and complement-like pathways, respectively. Proteins are bolded if their role in mosquito antifungal immunity is supported experimentally. Other key factors of the mosquito immune modules are listed in gray.