TABLE 1.
Cytokines in Drosophila immunity
| Cytokine/cytokine‐like | Tissue | Receptor | Pathway(s) affected/Immunomodulatory action | Mammalian or vertebrate homologue | References |
|---|---|---|---|---|---|
| Diedel (Die) | Fat body, induced and secreted upon infection | ND | Imd (a systemic negative regulator); Die mutant flies have reduced viability and succumb more rapidly than controls when infected with the RNA Sindbis virus | ND a | [252, 253 |
| Edin (elevated during infection) | Fat body, secreted into the haemolymph upon infection | ND | Edin mediates plasmatocyte self‐renew and proliferation; mobilization of sessile haemocytes; lamellocyte generation; induces encapsulation | ND | [89, 254, 255 |
| Eiger (eda‐like cell death trigger) | Imaginal discs, fat body, haemocytes, released in the haemolymph | Wengen | JNK; Eiger is a proinflammatory cytokine that strongly induces apoptotic cell death; drive apoptosis‐induced proliferation of imaginal discs epithelia via resident plasmatocytes; triggers activation of Toll signalling in the fat body when expressed in imaginal disc tumours and haemocytes; induces crystal cell rupture post injury and mediates melanization; activates phagocytosis to aid clearance of extracellular pathogens | A homolog of the mammalian tumour necrosis factor (TNF‐α) | [122, 256 |
| GBP (Growth‐blocking peptide) | Fat body, central nervous system, haemocytes, integument | Methuselah‐like 10 (Mthl10) d | JNK; inositol phosphate (IP3)/Ca2+ signalling cascade b and in turn activate phospholipase C; PVR/ERK pathway c , co‐ordinate switch between humoral and cellular immunity: activating phagocytosis and encapsulation, while inhibiting production and release of AMPs | The consensus GBP motif ‐C‐x(2)‐G‐x(4,6)‐G‐x(1,2)‐C‐[KR] shares a significant similarity with a motif in the mammalian epidermal growth factor (EGF) family | [172, 260, 261 |
| Pvfs (1–3) e | Embryonic haemocytes, expressed in many tissues partly redundantly | Pvr | PVR; inhibit humoral immune responses, while stimulating haemocytes spreading; Pvf‐1 activates resident plasmatocytes to recover the eye imaginal disc epithelium from tissue damage; Pvf‐2 is required for haemocyte proliferation and completion of normal lymph gland size; Pvf2 and Pvf3 control haemocyte viability and invasive migration | Drosophila Pvfs are akin to the mammalian PDGF/VEGF receptors | [172, 262 |
| Spätzle (Spz) | Haemocytes, other tissues? secreted into the haemolymph | The dimeric Toll | Spz binding to the Toll receptor activates the Toll pathway crucial for humoral immunity against Gram+ bacteria and fungi; Toll pathway activation leads to formation of lamellocytes during cellular immune response; Toll signalling in the fat body activates cellular immune defence events, like mobilization of sessile haemocytes, melanotic nodules formation, haemocyte proliferation; encapsulation and killing of the wasp larvae | Vertebrate NGF, mammalian IL‐17F | [121, 265, 266 |
| Unpaired (Upd) (Upd1, Upd2, Upd3) | Secreted from haemocytes, fat body (Upd2), expressed in larval lymph glands | Domeless (Dome) | JAK/STAT; Upd2 and Upd3 co‐ordinate different tissues for the cellular immune response, e.g., activate JAK/STAT signalling in somatic muscle which is necessary for lamellocyte formation and wasp egg encapsulation; Upd control haemocyte proliferation during wounding and restricting tumour growth; Upd released by haemocytes co‐ordinate the wound‐healing program in the gut via stimulating intestinal stem cell proliferation and immune response | Mammalian type I cytokines and vertebrate leptin‐like (interleukin 6 (IL‐6) family) | [110, 123, 267, 268 |
| WntD (Wnt inhibitor of Dorsal) | Early embryo | Frizzled (Fz)4 | WntD negatively regulates both the Toll (a feedback inhibitor of Dorsal/NF‐κB in embryos during both embryonic patterning and immune response) and the Imd pathway in adult flies; WntD‐deficiency rendered flies are more susceptible to Listeria monocytogenes infection | Vertebrate Wnt8 proteins | [253, 254, 269 |
Abbreviation: ND, not determined.
a
Die belongs to a larger family that includes homologs that can be found in genomes of members of three unrelated families of large DNA viruses that infect lepidopterans, the Entomopoxviridae, Baculoviridae and Ascoviridae. Die homologs are also present in the venom of two related parasitoid wasp species, Leptopilina boulardi and L. heterotoma [252].
b
GBP also acts through the phospholipase C (PLC)/Ca2+ signalling cascade to mediate the secretion of Pvf [260].
c
A receptor‐regulated kinase cascade.
d
G protein‐coupled receptor.
e
Pvf: a ligand for platelet‐derived growth factor (PDGF)‐ and vascular endothelial growth factor (VEGF)‐receptor (Pvr) homologue.