Immunomodulatory Properties of HLA-G in Infectious Diseases

Table 1

Summary of the main studies on HLA-G and infectious diseases.

	HLA-G level changes			Model or patients	Characteristics	References
	Cell surface	Cell surface	Blood sHLA-G
	Increase	Decrease	Increase
Infectious nonviral diseases
Septic shock			↗	𝑛=64	Marked early and persistent increase: predictor of survival	[47]
Parasitic infections due to; Plasmodium falciparum
		↘		Malaria-infected placenta (𝑛=15)	Extravillous trophoblast cells (42% versus 90% in controls); Association with an increase in NK cells	[118]
Leishmania infantum; visceral leishmania (VL)			↗	𝑛=94; 31 HIV+; 24 VL (7 HIV+ and 17 HIV−); 39 healthy subjects	HIV and VL: 57%; HIV alone: 81%; VL-HIV seronegative: 35%	[50]
Toxoplasma gondii	↗			In vitro infection of human trophoblast and BeWo cells	At 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 (𝑛=12)	Monocytes in treated patients; Expression on monocytes decreases after treatment to block; cytokines (IL-10)	[56]
	↗			Patients treated (𝑛=7) 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 (𝑛=10); Patients with HCMV pneumonitis	Day 20 poststimulation: expression in 45% of macrophages; Bronchoalveolar macrophages; Cooperative action of pp72 and pp86	[61]
	↗		↗	Patients (𝑛=75)	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 A549	Upregulation 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 (𝑛=79)	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 (𝑛=74)	Hepatocytes and biliary epithelial cells	[70]
Hepatitis C virus			↗	Chronic hepatitis C (𝑛=67)	sHLA-G = sHLA-G1 and-G5; Increase in plasma IL-10 and IFN-γ concentrations	[69]
	↗			Liver biopsies of patients with chronic hepatitis C (𝑛=89)	Hepatocytes; More frequent in milder stages	[121]
	↗			Liver biopsies of patients with chronic hepatitis C (𝑛=20)	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]