Traditionally, insects have been thought to be entirely dependent on their innate immune system, which has little capacity for the acquisition of experience from previous infections. However, much experimental evidence has challenged this view, showing that insects can develop long-term, pathogen-specific immune memory, which in some cases can be transmitted to offspring. Although significant progress has been made in this area, the underlying mechanism is still not fully understood, and a number of fundamental questions remain unanswered. In this review, we present an overview of documented cases of insect immune memory and summarize the experimental evidence in support of the prevailing hypotheses on the mechanism of antiviral and antibacterial immune memory in insects. We also highlight key questions that remain unanswered and discuss Drosophila melanogaster as a powerful model organism for investigating the mechanisms of innate immune memory formation. Finally, we evaluate the significance of this research and explore the potential for insect vaccination.

• Klíčová slova
• Dscam, evolutionary biology, hemocytes, immune memory, immunology, inflammation, insect immunity, insect vaccination, trained immunity,
• MeSH
• Drosophila melanogaster * imunologie   MeSH
• hmyz * imunologie   MeSH
• imunologická paměť * MeSH
• přirozená imunita * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

During parasitoid wasp infection, activated immune cells of Drosophila melanogaster larvae release adenosine to conserve nutrients for immune response. S-adenosylmethionine (SAM) is a methyl group donor for most methylations in the cell and is synthesized from methionine and ATP. After methylation, SAM is converted to S-adenosylhomocysteine, which is further metabolized to adenosine and homocysteine. Here, we show that the SAM transmethylation pathway is up-regulated during immune cell activation and that the adenosine produced by this pathway in immune cells acts as a systemic signal to delay Drosophila larval development and ensure sufficient nutrient supply to the immune system. We further show that the up-regulation of the SAM transmethylation pathway and the efficiency of the immune response also depend on the recycling of adenosine back to ATP by adenosine kinase and adenylate kinase. We therefore hypothesize that adenosine may act as a sensitive sensor of the balance between cell activity, represented by the sum of methylation events in the cell, and nutrient supply. If the supply of nutrients is insufficient for a given activity, adenosine may not be effectively recycled back into ATP and may be pushed out of the cell to serve as a signal to demand more nutrients.

When confronted with an infection, immune cells are rapidly activated to fight the threat. However, like all cells, they require energy to act. While most cells reduce their activity when nutrients are scarce, the immune system cannot afford to do so, as halting its response could put the entire body at risk from infection. It is not clear how immune cells manage this complex nutritional budgeting. Previous studies of fruit fly larvae infected with a parasitoid wasp revealed that immune cells secure extra energy by releasing a molecule called adenosine. This slows the metabolism of non-immune tissues, leaving more nutrients available for immune cells. However, the exact mechanism that immune cells use to produce adenosine remained uncertain. To further examine this process, Nedbalova et al. – who are part of the research group that carried out the previous work – extracted activated immune cells from a parasitoid-infected larva and fed them a labelled amino acid. Tracing this label revealed an increase in the number of chemical units known as methyl groups that had been added to molecules within the cell. This process, known as methylation, can regulate metabolic activity within cells and produces adenosine as a byproduct. Further genetic studies showed that if nutrient supplies were sufficient, the immune cells recycled this adenosine back into ATP, the body’s main energy currency. This suggests that if there were not enough nutrients to do this, the excess adenosine would slow the metabolism of non-immune cells, therefore securing more nutrients for the immune cells. Therefore, Nedbalova et al. hypothesise that these two processes could form the basis of a feedback mechanism that allows the immune cells to regulate their energy demands. Taken together, the findings suggest that adenosine may act as a sensor to reflect immune activity, with it being released when the cells are stimulated and recycled if they have enough energy. This hypothesis still requires further testing but, as adenosine pathways are present across all organisms, it could have implications for many physiological and disease-related processes.

• Klíčová slova
• D. melanogaster, S-adenosylhomocysteinase, SAM transmethylation pathway, adenosine kinase, adenosine signaling, adenylate kinase, biochemistry, chemical biology, immunology, inflammation, privileged immunity,
• MeSH
• adenosin * metabolismus   MeSH
• adenosinkinasa metabolismus   MeSH
• adenosintrifosfát * metabolismus   MeSH
• Drosophila melanogaster * imunologie   parazitologie   metabolismus   růst a vývoj   MeSH
• larva imunologie   metabolismus   parazitologie   růst a vývoj   MeSH
• metylace MeSH
• S-adenosylmethionin * metabolismus   MeSH
• sršňovití MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adenosin * MeSH
• adenosinkinasa MeSH
• adenosintrifosfát * MeSH
• S-adenosylmethionin * MeSH

BACKGROUND: The metabolically demanding nature of immune response requires nutrients to be preferentially directed towards the immune system at the expense of peripheral tissues. We study the mechanisms by which this metabolic reprograming occurs using the parasitoid infection of Drosophila larvae. To overcome such an immune challenge hemocytes differentiate into lamellocytes, which encapsulate and melanize the parasitoid egg. Hemocytes acquire the energy for this process by expressing JAK/STAT ligands upd2 and upd3, which activates JAK/STAT signaling in muscles and redirects carbohydrates away from muscles in favor of immune cells. METHODS: Immune response of Drosophila larvae was induced by parasitoid wasp infestation. Carbohydrate levels, larval locomotion and gene expression of key proteins were compared between control and infected animals. Efficacy of lamellocyte production and resistance to wasp infection was observed for RNAi and mutant animals. RESULTS: Absence of upd/JAK/STAT signaling leads to an impaired immune response and increased mortality. We demonstrate how JAK/STAT signaling in muscles leads to suppression of insulin signaling through activation of ImpL2, the inhibitor of Drosophila insulin like peptides. CONCLUSIONS: Our findings reveal cross-talk between immune cells and muscles mediates a metabolic shift, redirecting carbohydrates towards immune cells. We emphasize the crucial function of muscles during immune response and show the benefits of insulin resistance as an adaptive mechanism that is necessary for survival.

• Klíčová slova
• Drosophila, Immunity, Insulin resistance, JAK/STAT signaling, Metabolism,
• MeSH
• Drosophila genetika   MeSH
• imunita MeSH
• inzulinová rezistence * MeSH
• Janus kinasy metabolismus   MeSH
• larva metabolismus   MeSH
• proteiny Drosophily * metabolismus   MeSH
• proteiny vázající IGF metabolismus   MeSH
• sacharidy MeSH
• sršňovití * metabolismus   MeSH
• svaly MeSH
• transkripční faktory STAT metabolismus   MeSH
• transkripční faktory metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ImpL2 protein, Drosophila MeSH Prohlížeč
• Janus kinasy MeSH
• proteiny Drosophily * MeSH
• proteiny vázající IGF MeSH
• sacharidy MeSH
• transkripční faktory STAT MeSH
• transkripční faktory MeSH

Cellular encapsulation associated with melanization is a crucial component of the immune response in insects, particularly against larger pathogens. The infection of a Drosophila larva by parasitoid wasps, like Leptopilina boulardi, is the most extensively studied example. In this case, the encapsulation and melanization of the parasitoid embryo is linked to the activation of plasmatocytes that attach to the surface of the parasitoid. Additionally, the differentiation of lamellocytes that encapsulate the parasitoid, along with crystal cells, is accountable for the melanization process. Encapsulation and melanization lead to the production of toxic molecules that are concentrated in the capsule around the parasitoid and, at the same time, protect the host from this toxic immune response. Thus, cellular encapsulation and melanization represent primarily a metabolic process involving the metabolism of immune cell activation and differentiation, the production of toxic radicals, but also the production of melanin and antioxidants. As such, it has significant implications for host physiology and systemic metabolism. Proper regulation of metabolism within immune cells, as well as at the level of the entire organism, is therefore essential for an efficient immune response and also impacts the health and overall fitness of the organism that survives. The purpose of this "perspective" article is to map what we know about the metabolism of this type of immune response, place it in the context of possible implications for host physiology, and highlight open questions related to the metabolism of this important insect immune response.

• Klíčová slova
• ROS, encapsulation, hemocyte, immunometabolism, lamellocyte, melanization, parasitoid wasp, phenoloxidase,
• MeSH
• buněčná diferenciace MeSH
• Drosophila melanogaster MeSH
• Drosophila * MeSH
• larva MeSH
• sršňovití * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH