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Regulation of Innate Immune Response to Fungal Infection in Caenorhabditis elegans by SHN-1/SHANK

  • Sun, Lingmei (Department of Pharmacology, Medical School of Southeast University) ;
  • Li, Huirong (Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Medical School, Southeast University) ;
  • Zhao, Li (Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Medical School, Southeast University) ;
  • Liao, Kai (Department of Pathology and Pathophysiology, Medical School of Southeast University)
  • Received : 2020.06.18
  • Accepted : 2020.09.08
  • Published : 2020.11.28

Abstract

In Caenorhabditis elegans, SHN-1 is the homologue of SHANK, a scaffolding protein. In this study, we determined the molecular basis for SHN-1/SHANK in the regulation of innate immune response to fungal infection. Mutation of shn-1 increased the susceptibility to Candida albicans infection and suppressed the innate immune response. After C. albicans infection for 6, 12, or 24 h, both transcriptional expression of shn-1 and SHN-1::GFP expression were increased, implying that the activated SHN-1 may mediate a protection mechanism for C. elegans against the adverse effects from fungal infection. SHN-1 acted in both the neurons and the intestine to regulate the innate immune response to fungal infection. In the neurons, GLR-1, an AMPA ionotropic glutamate receptor, was identified as the downstream target in the regulation of innate immune response to fungal infection. GLR-1 further positively affected the function of SER-7-mediated serotonin signaling and antagonized the function of DAT-1-mediated dopamine signaling in the regulation of innate immune response to fungal infection. Our study suggests the novel function of SHN-1/SHANK in the regulation of innate immune response to fungal infection. Moreover, our results also denote the crucial role of neurotransmitter signals in mediating the function of SHN-1/SHANK in regulating innate immune response to fungal infection.

Keywords

References

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