House dust mite extract primes Drosophila melanogaster host defense against microbial infections through two distinct mechanisms

Allergen immunotherapy directly addresses the biological cause of allergies like those causing asthma. For perennial allergies, the treatment involves exposure to house dust mite (HDM) extracts that aim to block T helper 2 responses. Here, we investigate whether exposure to HDM extracts affects other aspects of innate host defenses against infection using the Drosophila genetic model organism. We find that pretreatment of flies with HDM extract injection provides a degree of protection against several types of microbial infections, namely Gram-negative and Gram-positive bacterial infections as well as fungal infections. Interestingly, this protection appears to be achieved through distinct mechanisms. The priming afforded by HDM extracts against Gram-negative bacteria is mediated via a mild induction of the Immune deficiency pathway. In contrast, the protection against a Gram-positive bacterium, Staphylococcus aureus, and some Aspergillus fumigatus mycotoxins involves the induction of host antioxidant defenses via Drosophila NRF2. We conclude that HDM extract appears to stimulate distinct host defenses that are differentially relevant according to the nature of the subsequent immune challenge. Future studies on the role of the host antioxidant responses in the Drosophila model will reveal how the host is able to cope with deleterious reactive oxygen species that may be generated during infections.