PMID- 34939104
OWN - NLM
STAT- MEDLINE
DCOM- 20220414
LR  - 20240308
IS  - 1460-2423 (Electronic)
IS  - 0959-6658 (Print)
IS  - 0959-6658 (Linking)
VI  - 32
IP  - 2
DP  - 2022 Mar 19
TI  - Antigen presenting cell response to polysaccharide A is characterized by the 
      generation of anti-inflammatory macrophages.
PG  - 136-147
LID - 10.1093/glycob/cwab111 [doi]
AB  - Polysaccharide A (PSA) is the immunodominant capsular carbohydrate from the gram 
      negative commensal microbe Bacteroides fragilis that has shown remarkable potency 
      in ameliorating many rodent models of inflammatory disease by eliciting 
      downstream suppressive CD4+ T cells. PSA is composed of a zwitterionic repeating 
      unit that allows it to be processed by antigen presenting cells (APCs) and 
      presented by MHCII in a glycosylation-dependent manner. While previous work has 
      uncovered much about the interactions between MHCII and PSA, as well as the 
      downstream T cell response, little is known about how PSA affects the phenotype 
      of MHCII+ APCs, including macrophages. Here, we utilized an unbiased systems 
      approach consisting of RNAseq transcriptomics, high-throughput flow cytometry, 
      Luminex analysis and targeted validation experiments to characterize the impact 
      of PSA-mediated stimulation of splenic MHCII+ cells. The data revealed that PSA 
      potently elicited the upregulation of an alternatively activated M2 macrophage 
      transcriptomic and cell surface signature. Cell-type-specific validation 
      experiments further demonstrated that PSA-exposed bone marrow-derived macrophages 
      (BMDMs) induced cell surface and intracellular markers associated with M2 
      macrophages compared with conventional peptide ovalbumin (ova)-exposed BMDMs. In 
      contrast to macrophages, we also found that CD11c+ dendritic cells (DCs) 
      upregulated the pro-T cell activation costimulatory molecule CD86 following PSA 
      stimulation. Consistent with the divergent BMDM and DC changes, PSA-exposed DCs 
      elicited an antigen-experienced T cell phenotype in co-cultures, whereas 
      macrophages did not. These findings collectively demonstrate that the PSA-induced 
      immune response is characterized by both T cell stimulation via presentation by 
      DCs, and a previously unrecognized anti-inflammatory polarization of macrophages.
CI  - (c) The Author(s) 2021. Published by Oxford University Press. All rights reserved. 
      For permissions, please e-mail: journals.permissions@oup.com.
FAU - Zhou, Julie Y
AU  - Zhou JY
AD  - Department of Pathology, Case Western Reserve University School of Medicine, 
      10900 Euclid Avenue, Cleveland, OH 44106-7288, USA.
FAU - Zhou, David
AU  - Zhou D
AD  - Department of Computer Science, Arizona State University, 1151 S. Forest Avenue, 
      Tempe, AZ 85281, USA.
FAU - Telfer, Kevin
AU  - Telfer K
AD  - Department of Pathology, Case Western Reserve University School of Medicine, 
      10900 Euclid Avenue, Cleveland, OH 44106-7288, USA.
FAU - Reynero, Kalob
AU  - Reynero K
AD  - Department of Pathology, Case Western Reserve University School of Medicine, 
      10900 Euclid Avenue, Cleveland, OH 44106-7288, USA.
FAU - Jones, Mark B
AU  - Jones MB
AD  - Department of Pathology, Case Western Reserve University School of Medicine, 
      10900 Euclid Avenue, Cleveland, OH 44106-7288, USA.
FAU - Hambor, John
AU  - Hambor J
AD  - Research Beyond Borders, Boehringer Ingelheim Pharmaceuticals, 900 Ridgebury 
      Road, Ridgefield, CT 06877, USA.
FAU - Cobb, Brian A
AU  - Cobb BA
AUID- ORCID: 0000-0003-1055-2530
AD  - Department of Pathology, Case Western Reserve University School of Medicine, 
      10900 Euclid Avenue, Cleveland, OH 44106-7288, USA.
LA  - eng
GR  - P30 CA043703/CA/NCI NIH HHS/United States
GR  - R01 AI154899/AI/NIAID NIH HHS/United States
GR  - R01 GM115234/GM/NIGMS NIH HHS/United States
GR  - T32 AI089474/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Glycobiology
JT  - Glycobiology
JID - 9104124
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Polysaccharides)
RN  - EC 3.4.21.77 (Prostate-Specific Antigen)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/metabolism
MH  - *Antigen-Presenting Cells/metabolism
MH  - Dendritic Cells
MH  - Humans
MH  - Macrophages
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Polysaccharides/metabolism
MH  - *Prostate-Specific Antigen/metabolism
PMC - PMC8934142
OTO - NOTNLM
OT  - RNAseq
OT  - immune regulation
OT  - macrophage
OT  - polysaccharide
OT  - transcriptomics
EDAT- 2021/12/24 06:00
MHDA- 2022/04/15 06:00
PMCR- 2022/11/22
CRDT- 2021/12/23 05:58
PHST- 2021/08/05 00:00 [received]
PHST- 2021/10/01 00:00 [revised]
PHST- 2021/10/16 00:00 [accepted]
PHST- 2021/12/24 06:00 [pubmed]
PHST- 2022/04/15 06:00 [medline]
PHST- 2021/12/23 05:58 [entrez]
PHST- 2022/11/22 00:00 [pmc-release]
AID - 6433003 [pii]
AID - cwab111 [pii]
AID - 10.1093/glycob/cwab111 [doi]
PST - ppublish
SO  - Glycobiology. 2022 Mar 19;32(2):136-147. doi: 10.1093/glycob/cwab111.