Different subsets of peripheral blood dendritic cells show distinct phenotypic and functional abnormalities in HIV-1...

To analyse the distribution, expression of chemokine receptors and ex vivo production of inflammatory cytokines by peripheral blood (PB) monocytes and DC in HIV-1+ individuals.

Dendritic cells (DC) play an important role in the establishment and dissemination of HIV infection. DC interaction with HIV depends on expression of HIV receptors and co-receptors. Accumulating evidence supports the notion that DC functionality is impaired in HIV-1+ patients.

PB samples from 30 naive-treated HIV-1+ progressors were studied. Additionally, 10 adult healthy volunteers (AHV), seven Hepatitis C virus positive (HCV+)/HIV-1- patients and five long-term non-progressor HIV-1+ patients (HIV-1+LTNP) were included as controls. Flow cytometry immunophenotyping was used for the identification, enumeration and characterization of monocytes and DC.

PB myeloid DC (mDC) and plasmacytoid DC (pDC) were significantly decreased in HIV-1+ progressors, while unaltered in HIV-1+LTNP. The expression of CXCR2 and CXCR4 and of CXCR4 and CCR5 were severely altered on PB mDC and pDC from HIV-1+ progressors, respectively. By contrast, both the expression of the chemokine receptors analysed and the numbers of CD16+ DC in HIV-1+ progressors were not different from AHV, while altered in HCV+/HIV-1- and HIV-1+LTNP. Furthermore, PB monocytes and DC from HIV-1+ progressors spontaneously produced inflammatory cytokines, in contrast with AHV.

These results support the existence of a selective interaction between HIV-1 and both mDC and pDC, associated with HCV co-infection-independent spontaneous production of inflammatory cytokines, reflecting the occurrence of in vivo activation of the immune system, which might further contribute to the impaired DC functionality.