Independent effects on cellular and humoral immune responses underlie genotype-by-genotype interactions between Drosophila and parasitoids

It is common to find abundant genetic variation in host resistance and parasite infectivity within populations, with the outcome of infection frequently depending on genotype-specific interactions. Underlying these effects are complex immune defenses that are under the control of both host and parasite genes. We have found extensive variation in Drosophila melanogaster's immune response against the parasitoid wasp Leptopilina boulardi. Some aspects of the immune response, such as phenoloxidase activity, are predominantly affected by the host genotype. Some, such as upregulation of the complement-like protein Tep1, are controlled by the parasite genotype. Others, like the differentiation of immune cells called lamellocytes, depend on the specific combination of host and parasite genotypes. These observations illustrate how the outcome of infection depends on independent genetic effects on different aspects of host immunity. As parasite-killing results from the concerted action of different components of the immune response, these observations provide a physiological mechanism to generate phenomena like epistasis and genotype-interactions that underlie models of coevolution. Author summary In many species individuals differ greatly in how resistant they are to infection. Resistance frequently depends on the combination of host and parasite genomes-a host which is resistant to one parasite genotype may be susceptible to a different genotype. This has important evolutionary consequences, maintaining genetic variation in populations and driving dynamic changes in the frequency of the genetic variants involved. To understand how differences in the immune response give rise to these genetic interactions, we have studied a parasitic wasp that lays its eggs within the larvae of the fruit fly Drosophila melanogaster. We found that some aspects of the immune response are affected by the host genome, some by the parasite genome, and some by the specific combination of host and parasite. However, no single component of the immune response could predict whether a host killed the parasite. Our results demonstrate how a complex interplay between host and parasite genomes controls different aspects of immunity, ultimately determining whether the host can resist infection.