腮腺炎病毒诱导小鼠睾丸天然免疫反应的机制细胞生物学专业论文.docxVIP

AbstractBackground Abstract Background and objectives：Mumps virus(MuV)infection is highly tropism to the testis and frequently causes orchitis，which may lead to male infertility．Although the intl．0duction ofvaccines effectively control the pandemic ofMuV,mumps orchitis has been recentlv recurred world．wide．Understanding the mechanisms underlying the innate immune responses to MuV infection and antiviral defense against MuV in the testis Can aid in the development of preventive and therapeutic approaches for mumps orchitis．This study aimed to investigate the MuV-induced innate immune responses in the mouse testis and MuV replication in testicular cells． Materials and methods：Primary testicular cells were isolated from C57BL／6 or Toll-like receptor(TLR)knockout(TLR2一，TLR3一，TLR4一一)mice．Virus titers were measured using crystal violet staining on Vero cells．Gene expression was examined using real-time quantitative RT-PCR．Cytokines level were measured using ELISA．Proteins were determined by Western blot，immunohistochemistry and immunofluorescence．Specific siRNA for target genes were used to knockdown gene expression． ResuIts：MuV induces innate immune responses in mouse Sertoli and Leydig cells through TLR2 and retinoic acid．inducible gene I(RIG-I)signaling，which result in the production ofproinflammatory cytokines and chemokines，including TNF一0【，IL-6，MCP一1，CXCL I O， and type 1 interferons(IFN．Ot and IFN．p)．By contrast，MuV does not induce the cytokine production in male germ cells．In response to MuV infection，Sertoli cells produce higher levels of proinflammatory cytokines and chemokines but lower levels of IFN-a and IFN一 13 than Leydig cells．The local injection of MuV into the testis triggers the testicular innate immune responses in vivo，and suppresses testosterone synthesis by Leydig cells． MuV can infect major testicular cells，including Sertoli，Leydig，macrophages，and germ cells．MuV differentially replicates in the testicular cells，which is associated with cell type．sp