Dendritic cells are antigen presenting cells of the innate immune system which produce various cytokines and uniquely prime naïve T cells to generate an adaptive immune response.(1,2) Consequently, this crafts an efficient immune attack to rid the human body of pathogens such as HIV-1. A study by Huang et al.(1) found that primary HIV-1 infection results in a compromised functionality of myeloid and plasmacytoid dendritic cell subpopulations.
Primary HIV-1 infection describes the initial highly dynamic relationship between HIV-1 and host interactions.(3) This is categorized by Fiebig et al.(3) into six stages; acute stage (III/ IV) and early stage (V/ VI) are the focus in this study. Acute stage is defined from the time of viral entry to completion of seroconversion (production of HIV-1 antibodies). It is characterized by high level viremia and initial innate defences (release of acute phase proteins, pro inflammatory cytokines, activation of natural killer cells) which is not sufficient to eradicate the virus.(1,3) Subsequent progression into early stage describes the period from seroconversion through to viral load set point.(3) Dendritic cell mediated cytotoxic T cell response is partially responsible for this reduction in viral RNA, which is an important prognostic marker for AIDS progression.(1,4)
An earlier study (5) reported infection, depletion and dysfunction in mDCs and pDCs in advanced stages of HIV -1 infection. It was yet to be clearly elucidated if these changes occurred earlier on in HIV-1 infection or were an end outcome from long term viral exposure. Huang et al. (1) have aimed at answering this important question as DC dysfunction causes immunosuppression which has implications for HIV vaccine strategies and disease progression.
17 primary HIV-1 infected patients ( 7 acute stage and 10 early stage ) had their whole blood samples extracted and analysed. The number of mDCs was found to be significantly reduced in primary HIV-1 infection compared to HIV-1 negative controls. This could be a due to HIV-1 infection and depletion of mDCs.(2) Alternatively it could be explained by the relocalization of mDCs to secondary lymphoid tissue as a result of antigen uptake.(2)
This finding implored the question: Could these decreased quantitative changes be attributed to qualitative and functional changes? To answer this question, authors mixed mDCs with allogenic T cells to test for their antigen presenting properties. mDCs showed a reduced ability to prime CD4 and CD8 T-cell responses in acute HIV-1 infection. HIV-1 has been previously reported to down regulate autophagy which impairs MHC-II restricted HIV-1 antigen presentation.(6) Furthermore causing replication of HIV-1 in DCs and increased viral transfection to T cells.(7)
Next, authors used a flow cytometry based approach to analyse cytokine secretion properties of mDCs. Interestingly, the amount of pro-inflammatory cytokine secretion for IL-12p70 and IL-6 was elevated in...