View Program - 63rd Annual Drosophila Research Conference

JAK/STAT is a highly conserved pathway, which plays a key role in immune response. In the case of Drosophila larvae, JAK/STAT signaling is involved in differentiation of hemocytes into lamellocyte to fight against parasitoid wasp infection (Leptipilina boulardi). This, in part, is mediated by the secretion of cytokines Upd2 and Upd3 from hemocytes, which activates JAK/STAT signaling in skeletal muscles; required for the efficient encapsulation and melanization of the wasp egg. Deletion of Upd2 and Upd3 leads to significant reduction in lamellocyte number, and therefore efficient immune response.

In times of food scarcity, or high metabolic demand tissues compete for the nutrients available. Parasitoid wasp infection leads to a redistribution of nutrients from surrounding tissues, such as muscles and fat body, to provide sufficient energy for immune response. This supports the ‘selfish’ or ‘privileged’ immune system hypothesis, as the immune cells are prioritized over other tissues to aid the survival of the animal. Reduction in carbohydrate uptake in peripheral tissues during infection is thought to be mediated by suppression of insulin signaling (IS) in these non-immune organs. Our findings show lower levels of pAkt in the larval fat body and skeletal muscles during infection, indicating IS suppression. We propose the reduction in IS observed is a result of Insulin resistance (IR) in these tissues. Furthermore, we suggest this IR occurs via Upd2 and Upd3 mediated activation of JAK/STAT in muscles leading to a systemic metabolic reprogramming during infection.

JAK/STAT mediated metabolic reprogramming during immune response