Plasmacytoid dendritic cells have divergent effects on HIV infection of initial target cells and induce a pro-retention phenotype.

Although HIV infection inhibits interferon responses in its target cells in vitro, interferon signatures can be detected in vivo soon after sexual transmission, mainly attributed to plasmacytoid dendritic cells (pDCs). In this study, we examined the physiological contributions of pDCs to early HIV acquisition using coculture models of pDCs with myeloid DCs, macrophages and the resting central, transitional and effector memory CD4 T cell subsets. pDCs impacted infection in a cell-specific manner. In myeloid cells, HIV infection was decreased via antiviral effects, cell maturation and downregulation of CCR5 expression. In contrast, in resting memory CD4 T cells, pDCs induced a subset-specific increase in intracellular HIV p24 protein expression without any activation or increase in CCR5 expression, as measured by flow cytometry. This increase was due to reactivation rather than enhanced viral spread, as blocking HIV entry via CCR5 did not alter the increased intracellular p24 expression. Furthermore, the load and proportion of cells expressing HIV DNA were restricted in the presence of pDCs while reverse transcriptase and p24 ELISA assays showed no increase in particle associated reverse transcriptase or extracellular p24 production. In addition, pDCs also markedly induced the expression of CD69 on infected CD4 T cells and other markers of CD4 T cell tissue retention. These phenotypic changes showed marked parallels with resident memory CD4 T cells isolated from anogenital tissue using enzymatic digestion. Production of IFNα by pDCs was the main driving factor for all these results. Thus, pDCs may reduce HIV spread during initial mucosal acquisition by inhibiting replication in myeloid cells while reactivating latent virus in resting memory CD4 T cells and retaining them for immune clearance.

Urinary placental growth factor in preeclampsia and fetal growth restriction: An alternative to circulating biomarkers?

AIM: To correlate plasma and urinary soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PIGF) in preeclampsia (PE) and fetal growth restriction (FGR) and assess the performance in detecting established disease. METHODS: A cross-sectional case-control study recruited 26-40 weeks gestation pregnancies into four clinical groups: normal pregnancy, PE, PE + FGR, and FGR. enzyme-linked immunosorbent assay (ELISA) measurements of urinary and plasma sFlt-1 and PlGF levels were performed. Urinary levels of sFlt-1 and PIGF were normalized to creatinine. Spearman's rank correlation was used to assess the association between plasma and urinary levels of sFlt-1 and PIGF, and receiver operating characteristic graphs were used to quantify the performance of each individual marker and their ratios in predicting normal versus pathological pregnancies affected by preeclampsia and/or FGR. RESULTS: There was a significant correlation between plasma PlGF and urinary PlGF (r = 0.718, P < 0.001) in all groups. In the pathological groups, plasma sFlt-1 and urinary sFlt-1 as well as plasma sFlt-1: PIGF ratio and urinary sFlt-1: PlGF ratio were higher, but plasma PIGF and urinary PlGF were lower when compared to normal pregnancy. Plasma PIGF and plasma sFlt-1: PlGF ratio was comparable in performance to urinary PlGF and urinary sFlt-1: PIGF ratio for the diagnosis of preeclampsia and/or FGR. CONCLUSION: Urinary PIGF can be used as an alternative to circulating biomarkers in preeclampsia and FGR. Plasma sFlt-1, PlGF and sFlt-1: PlGF ratio as well as urinary PIGF and sFlt-1: PlGF ratio can be used to differentiate between normal pregnancy and pregnancies complicated by preeclampsia and FGR.