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Open AccessArticle

Dendritic Cells and Myeloid Derived Suppressor Cells Fully Responsive to Stimulation via Toll-Like Receptor 4 Are Rapidly Induced from Bone-Marrow Cells by Granulocyte-Macrophage Colony-Stimulating Factor

1
Institute for Molecular and Cellular Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore
2
School of Health and Biomedical Sciences, RMIT, Bundoora, VIC 3083, Australia
3
Institute for Health and Sport, Victoria University, Melbourne, VIC 3011, Australia
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Vaccines 2020, 8(3), 522; https://doi.org/10.3390/vaccines8030522
Received: 1 September 2020 / Accepted: 7 September 2020 / Published: 12 September 2020
(This article belongs to the Special Issue Research on Innate Immunity and Inflammation)
Dendritic cells (DCs) are commonly generated from bone marrow (BM) progenitor cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) alone or in combination with interleukin 4 (IL-4). These cells are often harvested post day 5, when they acquire maturation markers and can stimulate T cells. Apart from DCs, myeloid derived suppressor cells (MDSCs) are also found within these cultures. However, little is known about the functional characteristics of DCs and MDSCs before day 5. Herein, using a murine model, it is shown that early DCs and MDSCs, even in cultures with GM-CSF alone, upregulate fully maturation and activation surface molecules in response to the toll-like receptor 4 (TLR4) ligand lipopolysaccharide (LPS) stimulation. Despite initially displaying lower marker expression levels, these cells efficiently induced T cell stimulation and cytokine production. Interestingly, Gr-1int MDSCs increased their T cell co-stimulatory activity upon TLR4 stimulation. Additionally, early DCs and MDSCs exhibited differential endocytic capacity for viral sized nanoparticles and bacterial sized microparticles. DCs internalized both particle sizes, whilst MDSCs only internalized the larger microparticles, with reduced endocytic activity over time in the culture. These findings have unveiled an important role for the rapid initiation of productive immunity by GM-CSF, with promising implications for future vaccine and DC immunotherapy developments. View Full-Text
Keywords: granulocyte-macrophage colony-stimulating factor; GM-CSF; dendritic cells; myeloid derived suppressor cells; MDSCs; bone marrow culture granulocyte-macrophage colony-stimulating factor; GM-CSF; dendritic cells; myeloid derived suppressor cells; MDSCs; bone marrow culture
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Kong, Y.Y.; Wilson, K.; Apostolopoulos, V.; Plebanski, M. Dendritic Cells and Myeloid Derived Suppressor Cells Fully Responsive to Stimulation via Toll-Like Receptor 4 Are Rapidly Induced from Bone-Marrow Cells by Granulocyte-Macrophage Colony-Stimulating Factor. Vaccines 2020, 8, 522.

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