HLA-G level changes Model or patients Characteristics References Cell surface Cell surface Blood sHLA-G Increase Decrease Increase Infectious nonviral diseases Septic shock ↗
Marked early and persistent increase: predictor of survival [47 ] Parasitic infections due toPlasmodium falciparum ↘ Malaria-infected placenta (
) Extravillous trophoblast cells (42% versus 90% in controls) Association with an increase in NK cells [118 ] Leishmania infantum visceral leishmania (VL) ↗
31 HIV+ 24 VL (7 HIV+ and 17 HIV−) 39 healthy subjectsHIV and VL: 57% HIV alone: 81% VL-HIV seronegative: 35% [50 ] Toxoplasma gondii ↗ In vitro infection of human trophoblast and BeWo cellsAt mRNA and protein levels. Treatment with IL-10 decreases HLA-G expression. [53 ] ↗ Amniotic fluid: 58 women infected 24 noninfected Significantly higher levels when the fetus is congenitally infected. [52 ] Viral infections HIV ↘ Cotransfection experiments on glioma cell line and macrophages Nef-independent, Vpu-dependent [119 ] ↗ Before HAART, correlated with viral clearance and increase in CD4+ T-cell levels. Decrease after treatment (36 months) Role of interferons and cytokines Increase in shedding [54 ] ↗ Infection treated (20) or not treated (3) Indirect induction by viral products and/or cytokines (IL-10) T lymphocytes and monocytes [57 ] ↗ Treated by HAART (
) Monocytes in treated patients Expression on monocytes decreases after treatment to block cytokines (IL-10) [56 ] ↗ Patients treated (
) with HAART or with a protease inhibitor regime or after HAART stopped Monocytes (50%) on HAART Increase with nucleoside reverse transcriptase inhibitors but not with protease inhibitors Decrease when HAART removed [58 ]
Longitudinal study in 24 infected patients In early phases, restored to normal level in chronic phases of untreated normal progressors and long-term nonprogressors Secretion by monocytes, dendritic cells Role of IL-10 [120 ] hCMV ↗ hCMV reactivation in in vitro activated macrophages (
) Patients with HCMV pneumonitis Day 20 poststimulation: expression in 45% of macrophages Bronchoalveolar macrophages Cooperative action of pp72 and pp86 [61 ] ↗ ↗ Patients (
) Increase on peripheral monocytes (6.3% versus 1.6%) Association with increase in plasma IL-10 concentration and no significant increase in IFN-γ concentration [62 ] Neurotropic virus (HSV-1 and RABV) ↗ In vitro infection of human neuron cell line (NT2-N)Activation of HLA-G transcription Cell surface expression during RABV infection but not during HSV-1 infection [63 , 64 ] Influenza virus (IAV) H1N1 ↗ In vitro IAV infection of human alveolar epithelial cell line A549Upregulation of HLA-G m RNA and proteins [65 ] ↗ (101) HIN1 patients (58 pandemic and 43 seasonal H1N1) Monocytes and T lymphocytes (T reg CD4CD25FOXP3) [66 ] HPV ↘ Biopsies of invasive cervical carcinoma (
) Low HLA-G5 expression in all HPV-related cases [67 ] Hepatitis B virus ↗ ↗ 90 acute, 131 chronic, and 152 resolved cases of hepatitis B Chronic > acute Resolved = normal Expression on monocytes and Treg [68 ] ↗ Chronic hepatitis B (
) Hepatocytes and biliary epithelial cells [70 ] Hepatitis C virus ↗ Chronic hepatitis C (
) sHLA-G = sHLA-G1 and-G5 Increase in plasma IL-10 and IFN-γ concentrations [69 ] ↗ Liver biopsies of patients with chronic hepatitis C (
) Hepatocytes More frequent in milder stages [121 ] ↗ Liver biopsies of patients with chronic hepatitis C (
) Significant correlation with the area of liver fibrosis HLA-G-positive cells are mast cells Soluble HLA-G secretion by human mast cells regulated by class I interferons [71 ]