Abstract
Background. Human dendritic cell-specific intracellular adhesion molecule-3 (ICAM3)-grabbing non-integrin (DC-SIGN) is a mannose-binding lectin that initiates interaction between dendritic cells and resting T-lymphocytes. DC-SIGN is highly expressed in placental tissue on dendritic cells and Hofbauer cells, and it is suggested that HIV may become adsorbed to DC-SIGN on Hofbauer cells as part of the mechanism of mother-to-child HIV transmission. A possible mechanism of transfer of the virus from the Hofbauer cells to the fetus is the subsequent adsorption to DC-SIGN-related molecules (DC-SIGNRs), present on immediately adjacent capillary vascular endothelium. However, data on DC-SIGN and DC-SIGNR expression in the placenta are few.Methods. Forty term placentas from HIV-positive mothers and 21 term placentas from HIV-negative mothers underwent immunohistochemistry staining for DC-SIGN and DC-SIGNR expression. Five random sets of 10 villi were assessed, and the average number of positive cells were counted in each case. In addition, where possible, maternal and cord blood viral loads and maternal CD4+ counts were performed in the HIV-positive group only.Results. The median maternal CD4+ count was 377 cells/µl and 27% of participants had undetectable viral loads; the median detectable viral load was 3.72 log. Most (97%) of the cord bloods tested in infants from HIV-positive mothers had lower than detectable viral loads. HIV-positive cases had significantly greater expression of both DC-SIGNRs (median values in HIV-positive cases, 14.5 positive cells/10 villi (pc/10villi), compared with 11 pc/10villi in HIV-negative cases, p=0.020) and DC-SIGN (median value in HIV-positive cases, 26.5 pc/10villi, compared with 23 pc/10villi in HIV-negative cases, p=0.037). DC-SIGNR expression was also noted in Hofbauer cells and decidual macrophages in addition to endothelium (reported currently). There was no difference in expression of DC-SIGN and DC-SIGNRs in patients with or without chorioamnionitis, but there was an inverse relationship between DC-SIGN and DC-SIGNR expression and maternal CD4+ counts in HIV-positive cases. Conclusion. Both DC-SIGN and DC-SIGNR expression were higher in placentas from HIV-positive mothers compared with HIV-negative cases. These lectins may be potential new therapeutic targets for preventing vertical transmission of HIV.
Highlights
Human dendritic cell-speci c intracellular adhesion molecule-3 (ICAM3)-grabbing non-integrin (DC-SIGN) is a mannose-binding lectin that initiates interaction between dendritic cells and resting T-lymphocytes
Two of the 40 HIV-positive patients tested positive for syphilis (Venereal Disease Research Laboratory (VDRL)-positive) and received treatment for this, while none of the HIVnegative mothers was VDRL-positive
We found an increase in DC-SIGN expression in placentas from HIVpositive patients, which may be due to the increased cytokine milieu
Summary
Human dendritic cell-speci c intracellular adhesion molecule-3 (ICAM3)-grabbing non-integrin (DC-SIGN) is a mannose-binding lectin that initiates interaction between dendritic cells and resting T-lymphocytes. A possible mechanism of transfer of the virus from the Ho auer cells to the fetus is the subsequent adsorption to DC-SIGN-related molecules (DC-SIGNRs), present on immediately adjacent capillary vascular endothelium. Forty term placentas from HIV-positive mothers and 21 term placentas from HIV-negative mothers underwent immunohistochemistry staining for DC-SIGN and DC-SIGNR expression. Where possible, maternal and cord blood viral loads and maternal CD4+ counts were performed in the HIV-positive group only. Most (97%) of the cord bloods tested in infants from HIV-positive mothers had lower than detectable viral loads. Ere was no di erence in expression of DC-SIGN and DC-SIGNRs in patients with or without chorioamnionitis, but there was an inverse relationship between DC-SIGN and DC-SIGNR expression and maternal CD4+ counts in HIV-positive cases. Both DC-SIGN and DC-SIGNR expression were higher in placentas from HIV-positive mothers compared with HIV-negative cases. Both DC-SIGN and DC-SIGNR expression were higher in placentas from HIV-positive mothers compared with HIV-negative cases. ese lectins may be potential new therapeutic targets for preventing vertical transmission of HIV
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