A toll receptor and a cytokine, Toll5A and Spz1C, are involved in toll antifungal immune signaling in the mosquito Aedes aegypti.

The fungal-specific immune response in the mosquito Aedes aegypti involves the Toll immune pathway transduced through REL1, a homologue of the NF-kappaB transcription factor Drosophila Dorsal. The Toll receptor and its ligand, Spätzle (Spz), link extracellular immune signals to the Toll intracellular transduction pathway. Five homologues to the Drosophila Toll (Toll1) receptor (Toll1A, Toll1B, Toll5A, Toll5B, and Toll4) and three homologues to the Drosophila cytokine Spätzle (Spz1A, 1B, and 1C) were identified from genomic and cDNA sequence data bases. Toll1A, Toll5A, Toll5B, and Spz1A were specifically induced in the mosquito fat body following fungal challenge. This transcriptional up-regulation was mediated by REL1. Spz1C was constitutively expressed in the mosquito fat body, whereas Spz1B and Toll4 were primarily expressed in ovarian tissues of female mosquitoes. The transcripts of Toll1B were only detected in early stages of mosquito embryos. RNA interference knock down of Toll5A and Spz1C resulted in two phenotypes of Aedes Toll/REL1 pathway deficiency: decreased induction of Aedes Serpin-27A following fungal challenge and increased susceptibility to the entomopathogenic fungus Beauveria bassiana. These data suggest that Toll5A and Spz1C function as cytokine receptor systems specific to the Toll receptor-mediated immune response following fungal challenge in the mosquito fat body.