PMID- 32932705 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201027 IS - 2076-393X (Print) IS - 2076-393X (Electronic) IS - 2076-393X (Linking) VI - 8 IP - 3 DP - 2020 Sep 12 TI - 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. LID - 10.3390/vaccines8030522 [doi] LID - 522 AB - 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-1(int) 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. FAU - Kong, Ying Ying AU - Kong YY AD - Institute for Molecular and Cellular Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore. FAU - Wilson, Kirsty AU - Wilson K AD - School of Health and Biomedical Sciences, RMIT, Bundoora, VIC 3083, Australia. FAU - Apostolopoulos, Vasso AU - Apostolopoulos V AUID- ORCID: 0000-0001-6788-2771 AD - Institute for Health and Sport, Victoria University, Melbourne, VIC 3011, Australia. FAU - Plebanski, Magdalena AU - Plebanski M AUID- ORCID: 0000-0001-6889-3667 AD - School of Health and Biomedical Sciences, RMIT, Bundoora, VIC 3083, Australia. LA - eng PT - Journal Article DEP - 20200912 PL - Switzerland TA - Vaccines (Basel) JT - Vaccines JID - 101629355 PMC - PMC7564202 OTO - NOTNLM OT - GM-CSF OT - MDSCs OT - bone marrow culture OT - dendritic cells OT - granulocyte-macrophage colony-stimulating factor OT - myeloid derived suppressor cells COIS- The authors declare no conflict of interest. EDAT- 2020/09/17 06:00 MHDA- 2020/09/17 06:01 PMCR- 2020/09/12 CRDT- 2020/09/16 01:00 PHST- 2020/09/01 00:00 [received] PHST- 2020/09/07 00:00 [accepted] PHST- 2020/09/16 01:00 [entrez] PHST- 2020/09/17 06:00 [pubmed] PHST- 2020/09/17 06:01 [medline] PHST- 2020/09/12 00:00 [pmc-release] AID - vaccines8030522 [pii] AID - vaccines-08-00522 [pii] AID - 10.3390/vaccines8030522 [doi] PST - epublish SO - Vaccines (Basel). 2020 Sep 12;8(3):522. doi: 10.3390/vaccines8030522.