title: Myeloid-derived suppressor cells in murine AIDS inhibit B-cell responses in part via soluble mediators including reactive oxygen and nitrogen species, and TGF-β.
abstract: Monocytic myeloid-derived suppressor cells (M-MDSCs) were increased during LP-BM5 retroviral infection, and were capable of suppressing not only T-cell, but also B-cell responses. In addition to previously demonstrating iNOS- and VISTA-dependent M-MDSC mechanisms, in this paper, we detail how M-MDSCs utilized soluble mediators, including the reactive oxygen and nitrogen species superoxide, peroxynitrite, and nitric oxide, and TGF-β, to suppress B cells in a predominantly contact-independent manner. Suppression was independent of cysteine-depletion and hydrogen peroxide production. When two major mechanisms of suppression (iNOS and VISTA) were eliminated in double knockout mice, M-MDSCs from LP-BM5-infected mice were able to compensate using other, soluble mechanisms in order to maintain suppression of B cells. The IL-10 producing regulatory B-cell compartment was among the targets of M-MDSC-mediated suppression.
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, United States.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Rastad
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, United States; Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, United States. Electronic address: William.R.Green@dartmouth.edu.
authors.forename: William R
authors.initials: WR
authors.lastname: Green
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D060151:B-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication; D007108:Immune Tolerance; D008297:Male; D051379:Mice; D016183:Murine Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000378:metabolism*; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology* / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta / Q000097:blood*
chemical_list: D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II
keywords: B cell; Breg; INOS; Monocytic MDSC; Nitric oxide; Peroxynitrite; Reactive nitrogen species; Reactive oxygen species; Superoxide; Suppression