Compare mDCs and pDCs between two distinct patients groups in acute HIV-1 infection

Understanding how the innate immune response affects the outcome of HIV-1 infection in acute HIV-1 infection will open opportunities for vaccine development that can utilize the innate immunity to enhance viral control with minimal pathogenesis. Dendritic cells (DCs) are particularly important innate immune cells and HIV-1 exploits DCs to enhance infection. Thus, DCs are a critical link between virus, CD4+ T-cells, and CD8+ T-cells. DCs are divided into two broad subsets, myeloid (mDC) and plasmacytoid (pDC), based on phenotype, function, and tissue localization. Although details of these subsets are debated and vary based on species, pDCs are specialized early type 1 interferon-secreting cells that initiate antiviral adaptive immune responses. mDCs differentiate from immature bone marrow (BM)-derived precursors and function as peripheral sentinels by transmitting antigen derived signals to draining lymph nodes (LN). mDCs secrete high levels of interleukin-12 (IL-12) and are key players in amplifying adaptive immune responses[1]. Early immune events during HIV infection are associated with the rate of subsequent disease progression. A role for DCs in controlling HIV-1 replication during primary infection has been difficult to assess, given the difficulties in finding individuals with acute HIV infection. The aim of this study is to study the relationship between DCs number in acute infection and disease progression.

To study the relationship between DCs and disease progression, we compared the pDC and mDC number in Fiebig stage III between the CD4 High, CD4 Low, and normal control groups. We found a higher pDC number in normal controls compared with the CD4 High and CD4 Low groups (Figure 1b). The pDC number between the CD4 High and the CD4 Low groups did not differ significantly (Figure 1b). However, mDCs were significantly lower in the CD4 Low relative to CD4 High and normal controls (Figure 1c). There was no statistically significant difference in the mDC number between the CD4 High and normal controls (Figure 1c). DC numbers were negatively correlated with HIV viral load (Table 2).

Our results are consistent with reports that DCs are markedly reduced in number during acute HIV-1 infection[6‐9], particularly pDCs. The mechanism behind the decline in pDC numbers in acute HIV infection is not clear. It could be because of apoptosis as a direct result of infection[10, 11] or mediated by TRAIL and Fas ligand–Fas interactions; it could be a consequence of compromised production of pDC precursors because of bone marrow infection; or it may reflect pDC migration to lymphoid tissues after HIV-induced activation.

mDCs express apolipoprotein B mRNA editing enzyme catalytic polypeptides (APOBECs), proteins that deaminate cytidine to uridine in nascent minus-strand viral DNA, blocking HIV replication[11, 12]. Mature mDCs increase APOBECG expression, explaining their relative resistance to HIV-1 infection. mDCs capture and process HIV-1, and present associated antigens to T-cells. Thus, the loss of mDCs may on the one hand decrease APOBECG expression. On the other hand, the loss of mDCs decrease their ability of capture and process HIV-1 and present associated antigen to T cells. Therefore, this may explain why the loss of mDC in acute HIV infection could lead to rapid disease progression.

In conclusion, we found that the loss of mDC rather than pDC from the blood during acute HIV infection is associated with rapid disease progression. However, key questions remain to be answered regarding tissue distribution, development, and functional regulation.