Unlike mature DCs, immature myeloid DCs are specialized to take up antigens at sites of infection. Following capture of antigens, immature DCs traffic to lymphoid tissues where they develop into mature DCs, which are potent stimulators of naive T cells owing upregulation of expression of MHC class II and co-stimulation molecules 17, 22
Distinct HIV interactions with immature and mature dendritic cells (DCs)
HIV transmission efficiency can be enhanced by maturation of DCs9, 30, 58, 103
, suggesting that mature DCs in lymphoid tissues may facilitate infection of lymphoid-tissue-resident CD4+
T cells. However, the mechanisms underlying this increased viral transmission have not been well defined. Downmodulation of antigen uptake and degradation in mature DCs, as well as more efficient interactions between mature DCs and T cells may contribute to the enhanced HIV transmission efficiency 9, 58
. Depending on the activating signals they receive, immature DCs can develop into different subsets of mature DCs with differing capabilities in HIV transmission and T-cell activation58
. Increased ICAM1 expression correlates with the increased viral transmission by mature DC subsets, possibly due to stronger DC-T-cell interactions through ICAM1 binding to T-cell-expressed leukocyte function-associated molecule 1 (LFA1) 58
(). Moreover, different cellular trafficking of HIV within immature DCs and mature DCs may also contribute to differences in HIV transmission potential (L.W. and V.N.K., unpublished observations). Consistent with this, mature DCs have been reported to contain high levels of intact virions in large vesicular compartments with a perinuclear localization, whereas immature DCs retain few intact virus particles in endosomes close to the plasma membrane 106
DC maturation is associated with a diminished ability to support HIV replication, being 10- to 100-fold lower than immature DCs 30, 42
(). But, HIV-pulsed mature DCs have been shown to contain 15-fold more viral DNA than immature DCs, which initially suggested that virus entry was not impaired 42
. However, a recent study indicated that the defect in HIV replication observed in mature DCs results at least partially from decreased viral fusion 104
. By analysing the phases of viral replication, Bakri et al.
reported that DC maturation does not affect HIV reverse transcription, nuclear import and integration, suggesting that the reduced viral replication in mature DCs is due to post-integration blocks at the transcriptional level 105
. This might account for the high levels of viral DNA detected in mature cells but their inefficient release of viral virions.