Pattern Recognition Receptor-mediated Innate Immune Response In Mouse Seminal Vesicles

Backgrounds and objectives:The seminal vesicles(SV)are main male accessory sexual gland that produce about 70%of seminal liquid.The SV can be infected by microorganisms,thus leading to seminal vesiculitis that usually results in male infertility.However,the mechanism of microbial infection induced seminal vesiculitis have yet to be investigated,and the relationship between pattern recognition receptor(PRR)and seminal vesiculitis are not reported up to now.The recent study aims to indentify the mechanism of PRR-initated SV inflammatory responses using mouse isolated seminal vesicles epithelial cells(SVECs).Materials and methods:Isolated SVECs from 8-week-old male mouse,and challaged them with 3 kinds of microbiomimetic substance,including LPS,poly(I:C)and HSV60.The mRNA level of SVECs genes was tested using real-time qRT-PCR,while the protein level was determined by Western blotting and the secration of immunoregulatory cytokines was analysed using ELISE.TLR3-/-,TLR4-/-,IPS-1-/-and STING-/-gene knockout mice were used in indentifying the function of PRR in SVECs immune response regulation.Results:A number of PRRs were expressed in SVECs,including TLR3,TLR4,MDA5 and p204,and all of these PRRs could be activated by their legands LPS,poly(I:C)and HSV60,respectively.LPS could upregulate the expression of pro-inflammatory cytokines,such as TNF-a and IL-6,chemokines MCP-1 and CXCL-10,through NF-?B activation.However,HSV60 induced the expression of type 1 interferon(IFN),including IFN-a and IFN-?,and several kinds of antiviral proteins,through the activation of IRF3.Poly(I:C)could upregulate the expression of pro-inflammatory cytokines,chemokines,type 1 IFNs and antiviral proteins,through NF-?B and IRF3 activation.Moreover,TLR4,TLR3 and IPS-1,and STING,have significant effects in LPS-,poly(I:C)-,and HSV60-initiated innate immune response in mouse SVECs,respectively.PRR-intiated immune reponses,especially LPS-and poly(I:C)-induced innate responses may influence the function of SVECs,which increased the expression of the key rate-limiting enzymes for prostaglandin synthesis,mPGES and COX2,and decreased the expression of semenogelin,Sg-1.Conclusions:(1)The SVECs could recognised becteria,RNA virus and DNA virus,and activated self-inmune response to resist the invading microorganisms through PRRs.(2)PRR-initiated innate immune response affect the function of SVECs,which may affect male reproduction.