RRC ID 33048
Author Tsuzuki S, Matsumoto H, Furihata S, Ryuda M, Tanaka H, Sung EJ, Bird GS, Zhou Y, Shears SB, Hayakawa Y.
Title Switching between humoral and cellular immune responses in Drosophila is guided by the cytokine GBP.
Journal Nat Commun
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.
Volume 5
Pages 4628
Published 2014-8-18
DOI 10.1038/ncomms5628
PII ncomms5628
PMID 25130174
PMC PMC5755975
MeSH Animals Calcium Signaling / physiology Cytokines / physiology* Drosophila Proteins / genetics Drosophila Proteins / physiology Drosophila melanogaster / immunology* Drosophila melanogaster / physiology* Gene Knockdown Techniques Immunity, Cellular / physiology Immunity, Humoral / physiology Insect Proteins / physiology* Receptor Protein-Tyrosine Kinases / genetics Receptor Protein-Tyrosine Kinases / physiology Type C Phospholipases / physiology Vascular Endothelial Growth Factors / genetics Vascular Endothelial Growth Factors / physiology
IF 12.121
Times Cited 41
Drosophila 8222R-2 8222R-3