
Taylor and Kimbrell 20 observed that mutating genes in the Toll and Imd pathways did not eliminate sexual dimorphism in defense against fungal infection. Our investigation focuses on the role of Toll and Imd pathways, which are key regulators of the immune response and are largely responsible for the systemic inducible expression of antimicrobial peptides 10, 11, 12. The fly may respond to penetration by the fungus through systemic immune responses, which include antimicrobial peptide expression, phenoloxidase activity, microbial phagocytosis by hemocytes, and hemocyte abundance. Once the fungus enters the fly cavity, death by infection may result from the fungus consuming nutrients in the hemolymph 23 or from toxins released by the fungus 24.

In addition, the trachea, reproductive tract, and gut can mount local immune responses 11. When fungal spores come into contact with fly epithelia, they encounter diverse antimicrobial peptides that are constitutively expressed and may impact spore germination as well as the ultimate survival of the fly 22. To resolve the relative roles of barrier defense and systemic immunity, our study employs two different inoculation techniques: inoculation by spray, which can be impacted by barrier defenses and grooming, and inoculation by injection, which transfers spores directly into the hemolymph. melanogaster have thicker cuticles that might have evolved because of their need for extra protection in fights with other males 21 in which males are likely to be wounded. It is possible that this sex difference in survivorship arose through cuticular differences, given that male D. bassiana spores were introduced to their cuticles. Indeed, Taylor and Kimbrell 20 observed lower survival in D. Sex differences in susceptibility to infection may depend on barrier defenses such as cuticle integrity and on behavioral defenses such as grooming. There is an initial barrier defense followed by the internal immune response after the fungus has penetrated the cuticle. In resisting fungal infections, there are two broad categories of defense that could be sexually dimorphic in insects. bassiana can aid biological control efforts, and may be particularly useful for biological control of female mosquitoes that vector human disease. Understanding sexual dimorphism in insect susceptibility to B. The fungal entomopathogen used in our study, Beauveria bassiana, is used in biological control 15, 16, 17, 18, 19. Improving our understanding of immune defense against fungal infections, especially in insect hosts, has implications for the biological control of mosquito vectors of human disease and insect crop pests. Most immune-defense studies in flies and in mammals have focused on responses to bacterial infections, while defense against fungal infections remains understudied in comparison. Innate immunity is the first line of defense against pathogenic infections. melanogaster is an established genetic model that shares innate immune response pathways with mammals 10, 11, 12, 13, 14. The laboratory fruit fly, Drosophila melanogaster, can be used as a model organism to study sex differences in immune defense. However, the mechanistic and genetic bases for sex differences in infection-susceptibility have not been well-characterized. Dimorphism between the sexes can also affect host-parasite interactions, and sex differences in susceptibility to infection have been previously reported 3, 4, 5, 6, 7, 8, 9. Physiology and lifespan differ between females and males across many animal species 1, 2.

bassiana presents opportunities to further dissect its mechanistic details, with applications for biological control of insect vectors of human disease and insect crop pests. Surprisingly, loss of function mutation of relish, a gene in the Imd pathway, also removes the dimorphism, but the dimorphism persists in flies carrying other Imd pathway mutations. Loss of function mutations of Toll pathway genes remove the dimorphism in survivorship.

The sexual dimorphism is not exclusively due to barrier defenses and persists when flies are inoculated by injection as well as by surface exposure. Here we show that Drosophila melanogaster females are more likely than males to die from infection with several strains of the fungal entomopathogen Beauveria bassiana. The magnitude and direction of the sexual dimorphism in immune function varies greatly and the genetic and mechanistic bases for this dimorphism are often unknown. In many animal species, females and males differ in physiology, lifespan, and immune function.
