Paradoxes in the Phenotype, Frequency and Roles of Myeloid-Derived Suppressor Cells During HIV Infection

Figures & data

Table 1 Cell Surface Markers for Human MDSCs

Phenotype	Human MDSCs
	mMDSC	gMDSC
CD11b	+	+
HLA-DR	Low/–	Low/–
CD14	+	-
CD15	-	+
CD16	High	Int.
Lin	-	-
CD125	+	+
CD124	+	+
CD33	High	Int.
VEGFR1	±	+
CD83	-	-
CD66b	-	High

Table 2 Phenotypes of MDSCs and Their Mechanisms of Pathology During HIV Infection

Study Subjects	MDSC Markers	MDSC Phenotype	Role of MDSCs in HIV Pathogenesis	References
97 (HIV+ and controls)	CD11b^+CD14^−CD33^+CD15^+	gMDSC expanded	Elevated viral load, low CD4 count and increased Tregs	[^Citation23]
18 HIV+	CD14^highCD16^neg CCR2^low/neg	mMDSC expanded	Dampen expansion of CD8+ T cells	[^Citation16]
112 (HIV+ and controls)	HLA-DR^−/low CD11b^+ CD33^+/high CD14^+CD15^−	mMDSC expanded	Increased viral load, low CD4+ T cell, elevated arginase 1	[^Citation17]
37 HIV+	CD15^+CD33^+/dim CD11b^+	gMDSC expanded	High levels of PD-L1, T cell exhaustion	[^Citation24]
10 (HIV+ and controls)	CD11b^+CD33^+CD14^+HLA-DR^−/lo	mMDSC expanded	Increased IL-10, Tregs and T cell Suppression	[^Citation18]
105 HIV+	HLA-DR^lowCD11b^+ CD33^+CD15^+	gMDSC expanded	Lower CD3ζ level, induce T-cell anergy	[^Citation25]
67 (HIV/HCV and controls)	HLA-DR^_/low CD11b^+ CD33^+ CD14^+CD15^−	mMDSC expanded	Inflammation due to persistent activated T cells	[^Citation19]
138 children	HLADR^_/lowCD11b^+CD33^+ CD14^+CD15^−	mMDSC expanded	High IDO expression	[^Citation20]]
16 HIV+	CD11b^+CD33^+CD14^+HLA DR^−/lo	mMDSC expanded	Control production of IFNγ, induction of IL-10	[^Citation21]
12 macaques with SHIV	HLA-DR^lowCD11b^+ CD33^+CD14^+ or CD15^+	mMDSC expanded in the periphery but decreased in BM	Low MDSC in BM favors pathologic immune activation	[^Citation22]
19 rhesus macaques	CD3^− HLA-DR^− CD11b^+CD66^+	gMDSC expanded	Suppression of CD4+ and CD8+ T cell proliferation	[^Citation26]
60 HIV patients	HLA-DR^lowCD11b^+ CD33^+CD14^−CD15^+	gMDSC expanded	Low gMDSC (<6%) correlated to high viral load	[^Citation27]

Vollbrecht T, Stirner R, Tufman A, et al. Chronic progressive HIV-1 infection is associated with elevated levels of myeloid-derived suppressor cells. AIDS. 2012;26(12):F31–7. doi:10.1097/QAD.0b013e328354b43f22526518

 PubMedGoogle Scholar

Gama L, Shirk EN, Russell JN, Carvalho KI, Li M, Queen SE. Expansion of a subset of CD14highCD16negCCR2low/neg monocytes functionally similar to myeloid-derived suppressor cells during SIV and HIV infection. J Leukoc Biol. 2012;91(5):803–816. doi:10.1189/jlb.111157922368280

 PubMedGoogle Scholar

Qin A, Cai W, Pan T, et al. Expansion of monocytic myeloid-derived suppressor cells dampens T cell function in HIV-1-seropositive individuals. J Virol. 2013;87(3):1477–1490. doi:10.1128/JVI.01759-1223152536

 PubMedGoogle Scholar

Bowers NL, Helton ES, Huijbregts RP, Goepfert PA, Heath SL, Hel Z. Immune suppression by neutrophils in HIV-1 infection: role of PD-L1/PD-1 pathway. PLoS Pathog. 2014;10(3):1–9. doi:10.1371/journal.ppat.1003993

 Google Scholar

Garg A, Spector SA. HIV type 1 gp120–induced expansion of myeloid derived suppressor cells is dependent on interleukin 6 and suppresses immunity. J Infect Dis. 2014;209(3):441–451. doi:10.1093/infdis/jit46923999600

 PubMed Web of Science ®Google Scholar

Tumino N, Turchi F, Meschi S, Lalle E, Bordoni V, Casetti R. In HIV-positive patients, myeloid-derived suppressor cells induce T-cell anergy by suppressing CD3ζ expression through ELF-1 inhibition. AIDS. 2015;29(18):2397–2407. doi:10.1097/QAD.000000000000087126355672

 PubMedGoogle Scholar

Lei AH, Yang Q, Cai WP, Liu YF, Lan Y, Qin AP. Clinical significance of myeloid-derived suppressor cells in human immunodeficiency virus-1/hepatitis C Virus-coinfected patients. Scand J Immunol. 2016;83(6):438–444. doi:10.1111/sji.1242926972443

 PubMedGoogle Scholar

Plessis ND, Jacobs R, Gutschmidt A, et al. Phenotypically resembling myeloid derived suppressor cells are increased in children with HIV and exposed/infected with Mycobacterium tuberculosis. Eur J Immunol. 2017;47(1):107–118. doi:10.1002/eji.20164665827861788

 PubMedGoogle Scholar

Garg A, Trout R, Spector SA. Human immunodeficiency virus type-1 myeloid derived suppressor cells inhibit cytomegalovirus inflammation through interleukin-27 and B7-H4. Sci Rep. 2017;7(1):1–15. doi:10.1038/srep4448528127051

 PubMedGoogle Scholar

Sui Y, Frey B, Wang Y, et al. Paradoxical myeloid-derived suppressor cell reduction in the bone marrow of SIV chronically infected macaques. PLoS Pathog. 2017;13(5):1–28. doi:10.1371/journal.ppat.1006395

 Google Scholar

Dross SE, Munson PV, Kim SE, et al. Kinetics of myeloid derived suppressor cell frequency and function during SIV infection, combination antiretroviral therapy and treatment interruption. J Immunol. 2017;198(2):757–766. doi:10.4049/jimmunol.160075927974456

 PubMedGoogle Scholar

Agrati C, Tumino N, Bordoni V, et al. Myeloid derived suppressor cells expansion persists after early ART and may affect CD4 T cell recovery. Front Immunol. 2019;10:1–10. doi:10.3389/fimmu.2019.0188630723466

 PubMedGoogle Scholar