Development of human dendritic cells and their role in HIV infection: antiviral immunity versus HIV transmission

Abstract

Although dendritic cells (DCs) represent a small cell population in the body, they have been recognized as professional antigen presenting cells and key players of both innate and acquired immunity. The recent expansion of basic knowledge concerning differentiation and function of various DC subsets will greatly help to understand the nature of protective immunity required in designing acquired immunodeficiency syndrome (AIDS) vaccines. However, human immunodeficiency virus (HIV) not only targets CD4+ T cells but also myeloid cells, including macrophages and DC. When HIV infects DC, its replication is highly restricted in DC. Nevertheless, even a low level of HIV production is sufficient to enhance HIV replication in activated CD4+ T cells, through antigen presentation activity by HIV-infected DC. Considering how antiviral immunity is initiated and memory response is maintained, such efficient DC–T cell transmission of HIV should play an important role in the disturbed immune responses associated with HIV infection. Recently, accessory proteins encoded by HIV have been shown to interact with various proteins in DC, and thereby affect DC–T cell transmission. In this review, we summarize the current understanding about DC biology, antiviral immune responses and DC restriction factors, all of which will be important issues for the development of an effective AIDS vaccine in the future.

HIV-1-Induced Impairment of Dendritic Cell Cross Talk with γδ T Lymphocytes

“…Notably, stimulation of HIV-DC with PAM in the absence of ␥␦ T cells did not decrease the percentage of infected DC, suggesting that PAM-activated lymphocytes and not the stimulus per se were responsible for the control of virus replication (data not shown). HIV exposure of DC results not only in productive infection of these cells but also in the transfer of the virus to susceptible CD4 ϩ T lymphocytes (16). To further investigate whether the suppressive effect of activated ␥␦ T cells on HIV spreading among DC could also regulate their efficiency of virus transfer to CD4 ϩ T lymphocytes, HIV-DC, exposed or not to PAM-stimulated ␥␦ T cells, were cocultured with preactivated CD4 ϩ ␣␤ ⌻ lymphocytes and the expression of p24 gag within the lymphocyte population was monitored.…”

“…Dendritic cells (DC) are among the first cells targeted by HIV at the mucosal sites and are actively involved in spreading the virus to susceptible CD4 ϩ T lymphocytes (16). Given their pivotal role in marshalling immune responses, these cells have been exploited by the virus to escape antiviral immunity.…”

Dendritic Cells in HIV/SIV Prophylactic and Therapeutic Vaccination

“…Upon activation of the TLR7 and 9 signaling pathway by viral infection, pDCs produce a large amount of type 1 interferon (IFN) with antiviral activity. Both mDCs and pDCs exhibit anti-viral capacity by secretion of cytokines, antigen presentation, and T cell activation [1,4].…”

Strongyloides stercoralis infection in marmosets: replication of complicated and uncomplicated human disease and parasite biology

“…The lack of available direct experimental evidence has led to the discussion of interesting immunological factors involved in S. stercoralis dissemination during human strongyloidiasis in patients with immunosuppression caused by treatment with corticosteroids or by infection with the Human Immunodeficiency Virus (HIV) or Human T-Lymphotropic Virus type 1 (HTLV-1). The immunosuppression induced by viruses and by the administration of this class of drug is similar because the immunological activity of the organism is affected primarily by interference with cell-mediated immunity [14][15][16]. Differences in the immunology of the HIV and HTLV-1 viruses in the host explain the increased number of cases of disseminated strongyloidiasis in patients with prior HTLV-1 infection.…”