Journal
VIROLOGY
Volume 499, Issue -, Pages 9-22Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2016.08.031
Keywords
Monocytic MDSC; B cell; Reactive oxygen species; Reactive nitrogen species; INOS; Superoxide; Peroxynitrite; Nitric oxide; Breg; Suppression
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Funding
- Public Health Service Grants from the National Institute of Health [CA-50157, P30 GM-10345]
- NIH grant [T32 AI007363]
- National Cancer Institute [CA23108]
- NIH/NCRR NIGMS COBRE [P20 (RR16437), P30 (GM103415)]
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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-beta, 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. (C) 2016 Elsevier Inc. All rights reserved.
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