title: Switching between humoral and cellular immune responses in Drosophila is guided by the cytokine GBP.
abstract: Insects combat infection through carefully measured cellular (for example, phagocytosis) and humoral (for example, secretion of antimicrobial peptides (AMPs)) innate immune responses. Little is known concerning how these different defense mechanisms are coordinated. Here, we use insect plasmatocytes and hemocyte-like Drosophila S2 cells to characterize mechanisms of immunity that operate in the haemocoel. We demonstrate that a Drosophila cytokine, growth-blocking peptides (GBP), acts through the phospholipase C (PLC)/Ca(2+) signalling cascade to mediate the secretion of Pvf, a ligand for platelet-derived growth factor- and vascular endothelial growth factor-receptor (Pvr) homologue. Activated Pvr recruits extracellular signal-regulated protein kinase to inhibit humoral immune responses, while stimulating cell 'spreading', an initiating event in cellular immunity. The double-stranded RNA (dsRNA)-targeted knockdown of either Pvf2 or Pvr inhibits GBP-mediated cell spreading and activates AMP expression. Conversely, Pvf2 overexpression enhances cell spreading but inhibits AMP expression. Thus, we describe mechanisms to initiate immune programs that are either humoral or cellular in nature, but not both; such immunophysiological polarization may minimize homeostatic imbalance during infection.
authors.affiliation: 1] Department of Applied Biological Sciences, Saga University, Saga 840-8502, Japan [2].
authors.forename: Seiji
authors.initials: S
authors.lastname: Tsuzuki
authors.affiliation: 1] Department of Applied Biological Sciences, Saga University, Saga 840-8502, Japan [2].
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Matsumoto
authors.affiliation: Department of Applied Biological Sciences, Saga University, Saga 840-8502, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Furihata
authors.affiliation: Department of Applied Biological Sciences, Saga University, Saga 840-8502, Japan.
authors.forename: Masasuke
authors.initials: M
authors.lastname: Ryuda
authors.affiliation: Department of Applied Biological Sciences, Saga University, Saga 840-8502, Japan.
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Inositol Signaling Section, NIEHS, NIH, DHHS, Research Triangle Park, North Carolina 27709, USA.
authors.forename: Eui Jae
authors.initials: EJ
authors.lastname: Sung
authors.affiliation: 1] Inositol Signaling Section, NIEHS, NIH, DHHS, Research Triangle Park, North Carolina 27709, USA [2] Calcium Regulation Section, NIEHS, NIH, DHHS, Research Triangle Park, North Carolina 27709, USA.
authors.forename: Gary S
authors.initials: GS
authors.lastname: Bird
authors.affiliation: Inositol Signaling Section, NIEHS, NIH, DHHS, Research Triangle Park, North Carolina 27709, USA.
authors.forename: Yixing
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Inositol Signaling Section, NIEHS, NIH, DHHS, Research Triangle Park, North Carolina 27709, USA.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Shears
authors.affiliation: Department of Applied Biological Sciences, Saga University, Saga 840-8502, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Hayakawa
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D016207:Cytokines / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology; D004331:Drosophila melanogaster / Q000276:immunology* / Q000502:physiology*; D055785:Gene Knockdown Techniques; D007111:Immunity, Cellular / Q000502:physiology; D056724:Immunity, Humoral / Q000502:physiology; D019476:Insect Proteins / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology; D010738:Type C Phospholipases / Q000502:physiology; D042442:Vascular Endothelial Growth Factors / Q000235:genetics / Q000502:physiology
chemical_list: D016207:Cytokines; D029721:Drosophila Proteins; D019476:Insect Proteins; C528169:Pvf2 protein, Drosophila; D042442:Vascular Endothelial Growth Factors; C000602870:growth-blocking peptide, Drosophila; C438368:Pvr protein, Drosophila; D020794:Receptor Protein-Tyrosine Kinases; D010738:Type C Phospholipases