Tissue communication in a systemic immune response ofDrosophila

Abstract

Several signaling pathways, including the JAK/STAT and Toll pathways, are known to activate blood cells (hemocytes) in Drosophila melanogaster larvae. They are believed to regulate the immune response against infections by parasitoid wasps, such as Leptopilina boulardi, but how these pathways control the hemocytes is not well understood. Here, we discuss the recent discovery that both muscles and fat body take an active part in this response. Parasitoid wasp infection induces Upd2 and Upd3 secretion from hemocytes, leading to JAK/STAT activation mainly in hemocytes and in skeletal muscles. JAK/STAT activation in muscles, but not in hemocytes, is required for an efficient encapsulation of wasp eggs. This suggests that Upd2 and Upd3 are important cytokines, coordinating different tissues for the cellular immune response in Drosophila. In the fat body, Toll signaling initiates a systemic response in which hemocytes are mobilized and activated hemocytes (lamellocytes) are generated. However, the contribution of Toll signaling to the defense against wasps is limited, probably because the wasps inject inhibitors that prevent the activation of the Toll pathway. In conclusion, parasite infection induces a systemic response in Drosophila larvae involving major organ systems and probably the physiology of the entire organism.

Subpopulation of Macrophage-Like Plasmatocytes Attenuates Systemic Growth via JAK/STAT in the Drosophila Fat Body

“…Consistent with the hematopoietic phenotype observed in hop Tuml mutants, active JAK/STAT signaling is required for differentiation of lamellocytes upon wasp infestation (36). Moreover, main players of the signaling such as upd2 and upd3 are upregulated in hemocytes upon immune challenges (37). During cellular immune responses, hemocytes induce upd ligands and secrete them to the hemocoel, where active propagation of JAK/STAT signaling in various tissues including the muscle, occurs.…”

“…Therefore, we reasoned that the Pxn and Hml have differential expressions in circulating and sessile hemocytes, and selective reduction in Hml subpopulation raises the Pxn subtypes in specific conditions. Overall increase of Drosophila hemocyte populations has been attributed to systemic immune signaling (37). To ratify the causal systemic molecule for the upsurge of remnant plasmatocyte upon Hml + hemocyte ablation, we performed whole-larva realtime quantitative polymerase chain reaction (RT-qPCR).…”

“…The JAK/STAT pathway is a common downstream target of upd3, and is known to be involved in innate immune responses including hemocyte proliferation and lamellocyte differentiation (36,37). Given that loss of Hml + hemocytes induces upd3 expression in hemocytes, we next examined the activity of JAK/STAT signaling and its downstream target tissue upon loss of Hml + hemocytes.…”

“…Amongst target tissues, the activation of JAK/STAT signaling in the muscle is linked to insulin signaling and carbohydrate metabolism, directly coupling immunity and metabolism (38). Drosophila fat body is the main source for antimicrobial peptides (AMPs), which facilitate the humoral immune response (37)(38)(39) as well as for the orchestration of metabolic events to maintain internal energy balance during feeding or non-feeding states (39,40). Insulin production and secretion in the brain insulin producing cells (IPCs) is remotely controlled by the nutrient sensing from the fat body and vice versa, fat contents in the fat body is regulated by the insulin signaling (41,42).…”

Innate immune memory: An evolutionary perspective

“…Following parasitoïd wasp infection hemocytes secreted Upd2 and Upd3, two important cytokines leading to JAK/STAT activation that is required for an efficient encapsulation of wasp eggs. Toll signaling initiates a systemic response in which hemocytes are mobilized and activated…”