A putative C. elegans melatonin receptor is required for efficient pathogen clearance

Mcmullan, Rachel; Anderson, Alexandra; Chew, Yee Lian; Taylor-smith, Leanne; Schafer, William and May, Robin (2016). A putative C. elegans melatonin receptor is required for efficient pathogen clearance. In: Abstracts European Worm Meeting (EWM) 2016, p. 168.

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C. elegans defends itself from infection with pathogenic microbes by activating conserved signalling pathways that a play central roles in the host defences of mammals and insects. Although significant advances have been made in understanding how these pathways protect C. elegans the cell surface receptors that activate them during infection remain largely elusive.

G-protein coupled receptors (GPCRs) detect the presence of bacterial pathogens and regulate immune responses in worms, flies, mice and humans. Here I present data characterising the role of an orphan GPCR, f59d12.1, in the clearance of Microbacterium nematophilum infections from C. elegans. We have previously shown that EGL-30(Gq) signalling is required for the C. elegans response to infection with M. nematophilum. F59D12.1 acts upstream of, and in parallel to, this EGL-30 (Gαq) signalling pathway in epithelial cells to regulate pathogen clearance.

Genetic and pharmacological data identify melatonin as the ligand for F59D12.1. Melatonin synthesis in C. elegans is regulated by infection and melatonin signalling via F59D12.1 is required for efficient clearance of M. nematophilum infections. To our knowledge this is the first identification of a C. elegans melatonin receptor and the first demonstration of a role of melatonin signalling in C. elegans.
In mammals pathogen clearance is mediated by macrophages. We find that mammalian macrophages express orthologs of F59D12.1 suggesting that melatonin may be an evolutionarily conserved regulator of host defences. We are currently working to determine whether activation of mammalian melatonin receptors can enhance macrophage phagocytosis to promote pathogen clearance.

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