Solute Carrier Transporter SLC15A3 Participates Anti-viral Innate Immune Response

Objective SLC15A3,a membrane transport protein,has been reported to focus on its transport function,but the researches on its anti-viral innate immune response were very rare.In our previous work,we found that the high expression of SLC15A3 was significantly induced by herpes simplex virus 1(HSV-1)stimulation in human peripheral blood mononuclear cells(PBMCs).Therefore,this project would further explore the molecular mechanisms and signaling pathways of SLC15A3 in anti-viral innate immune response.Methods1.HSV-1 or vesicular stomatitis virus(VSV)or sendai virus(Se V)stimulated immune cells,such as T lymphocyte,B lymphocyte,monocyte,NK cell and dendritic cell isolated from PBMCs and or these cell lines,such as He La cell,Ha Ca T cell,THP1 cell and 293 T cell.Real-time fluorescence quantitative(PCR)and western blot(WB)were applied to analyze the expression of SLC15A3 in the above cells.2.Immunofluorescence(IF)experiment was used to examine the distribution of SLC15A3.3.Over-expression and silencing experiment were performed to observe the effects of SLC15A3 on viral replication and the induction of interferon.4.Co-Immunoprecipitation(Co-IP)was used to find SLC15A3 banding partners.Results1.SLC15A3 output was obviously increased after HSV-1 stimulation in B cells,monocytes,dendritic cells,He La cells,Ha Ca T cells,THP1 cells and 293 T cells;SLC15A3 output was also obviously increased after vesicular stomatitis virus(VSV)and sendai virus(Se V)stimulation in He La cells,Ha Ca T cells,THP1 cells and 293 T cells.2.SLC15A3 was found to localize to lysosome,mitochondrion,endoplasmic reticulum,peroxisome and late-endosome but not Golgi apparatus.3.SLC15A3 could increase IFN? and IL-29 production and suppress the replication of HSV-1,Se V and VSV.4.SLC15A3 could interact with the mitochondrial antiviral signaling protein(MAVS)and the stimulator of interferon genes(STING).Conclusion1.SLC15A3 in many immune cells,such as B cells,monocytes and dendritic cells might be induced by HSV-1;SLC15A3 in many cell lines,such as He La cells,Ha Ca T cells,THP1 cells and 293 T cells might be also induced by HSV-1,VSV and Se V.2.SLC15A3 might be localized to lysosome,mitochondria,peroxisome,late-endosome and endoplasmic reticulum.3.SLC15A3 might increase IFN output,such as IFN? and IL-29 production and inhibit replication of HSV-1,VSV and Se V.4.SLC15A3 might participate in MAVS and STING singnal pathways in anti-virus innate immune.