Genetics and Evolution of Drosophila Humoral Immunity against Parasitoid Infections

Abstract

The parasitoid wasp Leptopilina boulardi is a major natural parasite of Drosophila melanogaster. However, the regulation of Drosophila humoral immunity against parasitoids is not clearly illustrated. In this thesis, I investigated the humoral immune mechanisms underlying Drosophila resistance to parasitoid infections, as well as the evolution of humoral immunity in populations that evolved resistance under high parasite pressure. Natural populations differ in their resistance to parasitoid infections. To understand what causes these variations, I studied the cis-regulatory upstream region of lectin-24A, a gene found to be significantly induced specifically in the Drosophila larval fat body after parasitism. Using a fluorescent reporter driven by the lectin-24A upstream region, I found that a deletion largely abolished lectin-24A expression in some natural populations susceptible to parasitoid infections. Infection by parasitoids induces an immune response in Drosophila that consists of cellular and humoral defenses. I studied the mechanisms regulating the activation of humoral immunity after parasitism. Using the fluorescent reporter and RNA sequencing, I show that JAK/STAT, the GATA factor Pannier, and the NF-κB factor dorsal all modulate the expression of lectin-24A, suggesting their roles in the regulation of Drosophila humoral anti-parasitoid immunity in general. I also explored the role of a group of serine proteases that are consistently upregulated in Drosophila after parasitization with unknown roles in the anti-parasitoid response. I found that mutating one particular serine protease, CG43124, reduces the rate of successful melanotic encapsulations by the Drosophila larvae. Both constitutive and inducible immune mechanisms are utilized by hosts for defense. Constitutive immunity is predicted to be favored when parasite exposure is frequent. I show that this is indeed the case with Drosophila populations that have evolved resistance under high rates of parasitization. I also found that these populations evolved the ability to activate JAK/STAT signaling following infection, potentially due to the constitutive presence of Upd3 cytokine-expressing immature lamellocytes.