Dendritic cell subsets dynamics and cytokine production in SIVmac239-infected Chinese rhesus macaques

Abstract

BackgroundSeveral studies have demonstrated that SIV infection progresses more slowly to experimental AIDS in Chinese rhesus macaques (Ch Rhs) than in Indian rhesus macaques (Ind Rhs). Here we investigated the dynamic and functional changes in dendritic cell (DC) subsets in SIVmac239-infected Ch Rhs.ResultsThe numbers of both mDC and pDC strongly fluctuated but were not significantly changed during the acute and chronic phases of infection. However, the concentration of both poly (I:C)-induced IL-12 and HSV-1-induced IFN-α significantly increased in the acute phase of infection but returned to normal levels at the chronic phase of infection. The peak of IFN-α emerged earlier than that of IL-12, and it had a significantly positive correlation with IL-12, which indicated that IFN-α may initiate the immune activation. We also found that only the concentration of IFN-α was positively correlated with CD4+ T-cell counts, but it was negatively correlated with viral load.ConclusionHigh levels of IFN-α in the early stage of infection may contribute to effective control of virus replication, and normal levels of IFN-α during chronic infection may help Ch Rhs resist the disease progression. The change in DC subsets dynamics and cytokine production may help further our understanding of why Ch Rhs are able to live longer without progressing to an AIDS-like illness.

Inhibitory effects of chloroquine on the activation of plasmacytoid dendritic cells in SIVmac239-infected Chinese rhesus macaques

“…The SIVmac239-infected Chinese rhesus macaques were treated as previously described. 13 The SIVmac239-infected macaques were housed at the animal biosafety level-3 laboratory. The three macaques (00067, 00079 and 01035) that were found to have CD4 1 T-cell counts below 500 events per microliter were considered to be in the late infection stage while the others were considered to be chronically infected.…”

“…In the virion stimulation tests, the SIVmac239 virions were used at a p27 concentration of 200 ng/ml, while the herpes simplex virus (HSV) virions were used as previously described. 13 A chloroquine diphosphate salt (Sigma, Oakville, Ontario, Canada) solution was used in pDC activation tests at a concentration of 100 mM for 24 h and in T-cell activation tests at a concentration of 5 mM as described by Martinson et al 9 …”

“…The methods used for flow cytometry analysis of the dendritic cells and T cell subsets have been previously described. 13,14 Briefly, 50-ml whole blood samples were used in each analysis. After incubating blood samples with antibodies (Anti HLA-DR, CD123 antibodies for pDC while anti CD3, CD4 and CD8 antibodies for T cells) in the dark for 15 min, samples were treated with FACS lysing solution (BD Biosciences, San Jose, California, United States) for 10 min at room temperature.…”

High immune activation and abnormal expression of cytokines contribute to death of SHIV89.6-infected Chinese rhesus macaques

“…The viral load in plasma was measured by quantitative PCR for SIV gag RNA as described by Xia et al [45]. The probe and primers are listed in Supplementary Table S1.…”

Dynamics and functions of CD4+CD25high regulatory T lymphocytes in Chinese rhesus macaques during the early stage of infection with SIVmac239

“…Their absolute numbers were calculated from the absolute numbers of CD4 ? T cells (data shared, [29]). Although the number of Treg cells in different monkeys varied after challenge, a one-sample t-test analysis showed that the Treg cells increased significantly in the first month and remained at a high level (more than 11.06%) thereafter during the entire course of the study (p\0.01) ( Fig.…”