Dendritic Cell Numbers in the Blood of HIV-1 Infected Patients Before and After Changes in Antiretroviral Therapy

Abstract

Antigen presenting dendritic cells (DCs) can serve as sites for HIV replication and as vehicles for transmission of the virus to T cells. It is known that the numbers of DCs in blood is reduced during HIV-1 infection. Here we monitored the two major subsets of blood DCs in 12 individuals undergoing a change, primarily initiation, of highly active antiretroviral therapy. The numbers of plasmacytoid DCs were reliably higher on therapy, although in the 1-3 month interval we followed, these numbers did not return to those seen in HIV uninfected controls. An increase in plasmacytoid DCs was accompanied by an increase in IFN-alpha production in response to a standard challenge in culture with UV-inactivated herpes simplex virus. The levels of myeloid DCs also demonstrated an increase while on HAART, and these numbers become comparable to the HIV uninfected controls. The numbers of plasmacytoid and myeloid DCs varied inversely with the levels of plasma HIV viremia. These longitudinal studies extend prior work showing that virus infection with HIV leads to a decrease in the number of dendritic cells in blood, and that this can be reversed at least in part by therapy.

HIV Type 1 Infection Up-Regulates TLR2 and TLR4 Expression and Function in Vivo and in Vitro

“…The quantification of the cellular subpopulations was established to assess the possible differences between subject groups. In contrast to previous reports, 3 there was no significant change in the percentage or the absolute count of monocytes, pDCs, and mDCs in peripheral blood obtained from HIV-1-infected patients compared with healthy donors (data not shown). However, as expected, the CD4 + T cell counts were decreased in the HIV-1-infected patients, especially in those whose viral load was higher than 400 RNA copies/ml, indicating the immune alterations that are prevalent during HIV infection (Table 1 and Supplementary Fig.…”

“…1 Moreover, advanced HIV-1 infection is known to be associated with reduced innate response to new infectious challengers; indeed, HIV-1 infection can lead to markedly reduced numbers and altered functions of innate immune cells such as plasmacytoid dendritic cells (pDCs) and myeloid dendritic cells (mDCs). 2,3 Given the central role of DCs in linking innate and adaptive immunity, abnormalities or dysregulation of their function could help to explain the altered responses observed in HIV-1-infected subjects. DCs are activated through innate signaling receptors such as the toll-like receptors (TLRs) and by other members of pattern-recognition receptors (PRRs).…”

Differential Restoration of Myeloid and Plasmacytoid Dendritic Cells in HIV-1-Infected Children after Treatment with Highly Active Antiretroviral Therapy

“…Taken together with previous findings (14,15,21,35,36), the present findings suggest that HAART has a differential impact on the restoration of mDC and pDC subsets, which is simultaneously in accordance with the process of host immune reconstitution via augmentation of both the innate and adaptive immune responses. Thus, HAART treatment may establish a novel balance between the innate and adaptive immune responses, such that HAARTmediated recovery of innate immune function probably facilitates the increase of CD4 T cell percentage; however, further study needs to uncover the causative relationship between the recovery of DC subsets and the improvement of CD4 T cell and CTL response.…”

“…The significant positive correlation between pDC frequency and duration of HAART suggests that an extended period of antiviral therapy might be indicated to better restore circulating pDCs. It is noteworthy that recovery of pDCs was slower in our examined subjects than in adults in previous reports (15,35,36). This might be explained, in part, by differences in immune system plasticity between adults and children.…”

Dendritic cells from HIV-1 infected individuals are less responsive to toll-like receptor (TLR) ligands

“…Advanced HIV-1 infection is associated with diminished immune responses to pathogens. It is also associated with markedly reduced numbers and function of innate immune cells including plasmacytoid (pDC) and myeloid (mDC) dendritic cells (2)(3)(4)(5). The low number of pDC in chronic HIV-1 infection is associated with a diminished innate immune response and decreased levels of IFN-α production, which is also associated with an increased risk of opportunistic infections (3,6).…”