Journal article
Neuronal GPCR OCTR-1 regulates innate immunity by controlling protein synthesis in Caenorhabditis elegans
Scientific reports, Vol.6(1), pp.36832-36832
11/11/2016
Handle:
https://hdl.handle.net/2376/115535
PMCID: PMC5104976
PMID: 27833098
Abstract
Upon pathogen infection, microbial killing pathways and cellular stress pathways are rapidly activated by the host innate immune system. These pathways must be tightly regulated because insufficient or excessive immune responses have deleterious consequences. Increasing evidence indicates that the nervous system regulates the immune system to confer coordinated protection to the host. However, the precise mechanisms of neural-immune communication remain unclear. Previously we have demonstrated that OCTR-1, a neuronal G protein-coupled receptor, functions in the sensory neurons ASH and ASI to suppress innate immune responses in non-neural tissues against Pseudomonas aeruginosa in Caenorhabditis elegans. In the current study, by using a mass spectrometry-based quantitative proteomics approach, we discovered that OCTR-1 regulates innate immunity by suppressing translation and the unfolded protein response (UPR) pathways at the protein level. Functional assays revealed that OCTR-1 inhibits specific protein synthesis factors such as ribosomal protein RPS-1 and translation initiation factor EIF-3.J to reduce infection-triggered protein synthesis and UPR. Translational inhibition by chemicals abolishes the OCTR-1-controlled innate immune responses, indicating that activation of the OCTR-1 pathway is dependent on translation upregulation such as that induced by pathogen infection. Because OCTR-1 downregulates protein translation activities, the OCTR-1 pathway could function to suppress excessive responses to infection or to restore protein homeostasis after infection.
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Details
- Title
- Neuronal GPCR OCTR-1 regulates innate immunity by controlling protein synthesis in Caenorhabditis elegans
- Creators
- Yiyong Liu - Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, Spokane, Washington, USADurai Sellegounder - Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, Spokane, Washington, USAJingru Sun - Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, Spokane, Washington, USA
- Publication Details
- Scientific reports, Vol.6(1), pp.36832-36832
- Academic Unit
- Biomedical Sciences, Department of
- Publisher
- England
- Grant note
- P40 OD010440 / NIH HHS
- Identifiers
- 99900547322501842
- Language
- English
- Resource Type
- Journal article