Paradoxical myeloid-derived suppressor cell reduction in the bone marrow of SIV chronically infected macaques

PLoS Pathogens
Yongjun SuiJay A Berzofsky

Abstract

Myeloid derived suppressor cells (MDSCs), which suppress anti-tumor or anti-viral immune responses, are expanded in the peripheral blood and tissues of patients/animals with cancer or viral infectious diseases. We here show that in chronic SIV infection of Indian rhesus macaques, the frequency of MDSCs in the bone marrow (BM) was paradoxically and unexpectedly decreased, but increased in peripheral blood. Reduction of BM MDSCs was found in both CD14+MDSC and Lin-CD15+MDSC subsets. The reduction of MDSCs correlated with high plasma viral loads and low CD4+ T cell counts, suggesting that depletion of BM MDSCs was associated with SIV/AIDS disease progression. Of note, in SHIVSF162P4-infected macaques, which naturally control viral replication within a few months of infection, the frequency of MDSCs in the bone marrow was unchanged. To investigate the mechanisms by which BM MDSCs were reduced during chronic SIV infection, we tested several hypotheses: depletion due to viral infection, alterations in MDSC trafficking, and/or poor MDSC replenishment. We found that the possible mobilization of MDSCs from BM to peripheral tissues and the slow self-replenishment of MDSCs in the BM, along with the viral infection-induced depletion, all c...Continue Reading

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Citations

Nov 29, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ang LinKarin Loré
May 20, 2018·Hypertension·Sasha A FahmeRobert Peck
Feb 19, 2019·The Journal of Clinical Investigation·Yongjun SuiJay A Berzofsky
Sep 3, 2020·Frontiers of Medicine·Mahmoud Mohammad YaseenAmmar Daoud
May 30, 2019·Frontiers in Immunology·Monica VaccariGenoveffa Franchini
May 19, 2020·The Journal of Clinical Investigation·Anca DorhoiNelita du Plessis
Jan 23, 2018·Frontiers in Immunology·Anca Dorhoi, Nelita Du Plessis
Dec 21, 2018·Cancer Immunology, Immunotherapy : CII·Anca DorhoiAnnabel F Valledor

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Methods Mentioned

BETA
dissect
PCR

Software Mentioned

Graph Pad
Prism
FlowJo

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