Neuroendocrine signals modulate the innate immunity of Caenorhabditis elegans through insulin signaling

Trupti Kawli & Man-Wah Tan. Nat. Immunol. 9:1415-1424 (2008)

Speaker: Cheng-Yu Wang (王政育)                               Time: 14:10~15:00 May. 6, 2009

Commentator: Dr. Pei-Jane Tsai (蔡佩珍老師)              Place: Room 601

Abstract:

        Although there is the considerable evidence suggested communication or crosstalk between nervous and immune system¹, it is the issue remained to clarify. In this study, the authors used Caenorhabditis elegans infected with human opportunistic pathogen Pseudomonas aeruginosa (PA14) as the model to investigate the relationship between neuroendocrine signals and innate immunity. At first, they found mutant C. elegans with less neuronal excytosis had greater pathogen PA14 resistance than wild type. The dense core vesicles (DCVs) related gene unc-31 mutation also had the same result suggesting neuropeptide processing and secretion from DCVs are important in PA14 resistance. The PA14- GFP was used to evaluate the possible reason of PA14 resistance, and found less PA14 colonization in DCV mutant worms than wild type due to greater PA14 clearance. The real-time PCR analysis showed higher expression of immunity-related genes in DCV mutant worms. The sustained hypersecretion worms {goa-1 mutant or phorbol 12-myristate 13-acetate (PMA) treatment} have less PA14 resistance and greater PA14 colonization than wild type. The insulin-like signaling pathway is involved in the immune response of C. elegans².They further found sustained hypersecretion worms combined with insulin-like receptor DAF-2 mutation had recovery of PA14 resistance to wild type level. But DCV mutant worms combined with DAF-16 mutation (downstream of DAF-2) had lost PA14 resistance even worse than wild type. Some of upregulated genes in DCV mutant worms were regulated by DAF-16. INS-7 is a known DAF-2 agonist with neuronal and intestinal expression. The worms infected with virulent PA14 induced higher expression of ins-7, but not those with avirulent PA14. Worms with ins-7 mutation had greater PA14 resistance than wild type, and sustained hypersecretion worms combined with ins-7 mutation had recovery of PA14 resistance to be similar with wild type. The PA14 resistance of ins-7 mutant was involved with neuronal but not intestinal mutation of ins-7. In brief, INS-7 is a neuropeptide which regulated by neuronal secretion from DCVs and suppresses immune function by activating DAF-2 signaling to result in inhibition of DAF-16 and reduction of the expression of immunity-related genes in the intestine. This study provides the evidence that neurosecretory activity of DCVs can modulate antibacterial (PA14) immunity of C. elegans.

References:

1.      Brogden, K.A. et al. The nervous system and innate immunity: the neuropeptide connection. Nat. Immunol. 6, 558–564 (2005).

2.      Garsin, D.A. et al. Long-lived C. elegans daf-2 mutants are resistant to bacterial pathogens.Science 300, 1921 (2003).