{"doi":"10.1093/glycob/cwab111","title":"Antigen presenting cell response to polysaccharide A is characterized by the generation of anti-inflammatory macrophages","abstract":"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.","journal":"Glycobiology","year":2021,"id":186054,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9576,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":343782,"name":"David Zhou","orcid":"0000-0002-9635-0472","position":1,"is_corresponding":false},{"id":743313,"name":"Kevin Telfer","orcid":"0000-0002-1334-0931","position":2,"is_corresponding":false},{"id":744056,"name":"Kalob M. Reynero","orcid":null,"position":3,"is_corresponding":false},{"id":468871,"name":"Mark B. Jones","orcid":"0000-0002-0666-9245","position":4,"is_corresponding":false},{"id":218460,"name":"John Hambor","orcid":null,"position":5,"is_corresponding":false},{"id":468872,"name":"Brian A. Cobb","orcid":"0000-0003-1055-2530","position":6,"is_corresponding":false},{"id":566894,"name":"Julie Y. Zhou","orcid":"0000-0002-1533-5183","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-18T23:48:42.632147Z","pmid":"34939104","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}