The Dynamics Of Dendritic Cells In Peripherial Blood Of SHIV/SIV Infected Chinese Rhesus Macaques

Dendritic cells are professional antigen-presenting cells. The roles of dendritic cells in HIV infection have attracted more and more attention, however, the changes of DCs and their pathologocal roles in HIV/AIDS have not been fully addressed. In order to explore the variations of the number and function of DCs in HIV, we examined three subsets of DCs in peripheral blood of SHIV and SIV sequencially infected Chinese rhesus macaques, and the possible molecular mechanisms underlying DCs’ change.We used SHIV-SF162p4and SIVmac251sequencially to infect Chinese rhesus macaques through the rectum and vein and established a stable system infection. The number of DCs were detected by flow cytometry, then were compared in different groups criteria, for example, in different immunological subgroups, in different viral load groups, in different day points grouping, before and after Listeria bacteria immunization grouping. Moreover, we detected the maturation marker CD83and the expression of CD86and CCR7, then described the changes of these markers after LPS and R848. Whereafter, the RNA level of genes about DCs’ development and muturation such as IRF3, IRF7, IRF8, CRM1, E2-2were examined by TaqMan real time RT-PCR.According to our data, the virations of three subsets of DCs in HIV chronic infection period were different. HIV infection caused the number of CD11c+mDC and CD1c+mDC increase, while the number of CD123+pDC decrease. mDC decreased with the time, and pDC at different time points changed a little. CD11c+mDC increased with viral load, while CD123+pDC went by contrary. The number of CD123+pDC was highest in the immunological subgroup that had a protective effect. The maturation status of DCs also showed different characteristics. In infected animal CD11c+mDC showed incomplete maturation state, and CD1c+mDC, CD123+pDC presented the low mature state. After LPS stimulation, the maturation status of DCs had almost no change. However, after R848the maturation status of CD11c+mDC increased, but still lower than those in normal animal. At the same time, the maturation status of CD1c+mDC, CD123+pDC appeared only a small increase. The expressions of genes about DCs’ development and muturation in HIV infection and high risk group were higher than the normal group. The RNA levels of IRF7, CRM1that regulate DCs mature were increased after R848in accord with the conclution acquired by flow cytometry. The correlations between the levels of CD83molecules and genes were different in infected animal and normal animal, which validated that HIV led to the damage of the maturation of DCs.The infection of Chinese rhesus macaques inoculated SHIV/SIV by vein and mucosal routes was closer to people infected with HIV. These data indicated that HIV caused the number of mDC to increase, the number of pDC to decrease, then led the maturation state of DCs to destruct, and induced the expression of tolerance gene to increase. These data provided important information for the application of DCs vaccines for the treatment and prevention of HIV infection.