PMID- 34220742 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210706 IS - 1664-302X (Print) IS - 1664-302X (Electronic) IS - 1664-302X (Linking) VI - 12 DP - 2021 TI - Bifidobacterium breve Exopolysaccharide Blocks Dendritic Cell Maturation and Activation of CD4(+) T Cells. PG - 653587 LID - 10.3389/fmicb.2021.653587 [doi] LID - 653587 AB - Exopolysaccharide (EPS) is a bacterial extracellular carbohydrate moiety which has been associated with immunomodulatory activity and host protective effects of several gut commensal bacteria. Bifidobacterium breve are early colonizers of the human gastrointestinal tract (GIT) but the role of EPS in mediating their effects on the host has not been investigated for many strains. Here, we characterized EPS production by a panel of human B. breve isolates and investigated the effect of EPS status on host immune responses using human and murine cell culture-based assay systems. We report that B. breve EPS production is heterogenous across strains and that immune responses in human THP-1 monocytes are strain-specific, but not EPS status-specific. Using wild type and isogenic EPS deficient mutants of B. breve strains UCC2003 and JCM7017 we show that EPS had strain-specific divergent effects on cytokine responses from murine bone marrow derived macrophages (BMDMs) and dendritic cells (BMDCs). The B. breve UCC2003 EPS negative (EPS(-)) strain increased expression of cytokine genes (Tnfa, Il6, Il12a, and Il23a) relative to untreated BMDCs and BMDCs treated with wild type strain. B. breve UCC2003 and JCM7017 EPS(-) strains increased expression of dendritic cell (DC) activation and maturation marker genes (Cd80, Cd83, and Cd86) relative to untreated BMDCs. Consistent with this, BMDCs co-cultured with B. breve UCC2003 and JCM7017 EPS(-) strains engineered to express OVA antigen activated OVA-specific OT-II CD4(+) T-cells in a co-culture antigen-presentation assay while EPS proficient strains did not. Collectively, these data indicate that B. breve EPS proficient strains use EPS to prevent maturation of DCs and activation of antigen specific CD4(+) T cells responses to B. breve. This study identifies a new immunomodulatory role for B. breve EPS and suggests it may be important for immune evasion of adaptive immunity by B. breve and contribute to host-microbe mutualism. CI - Copyright (c) 2021 Hickey, Stamou, Udayan, Ramon-Vazquez, Esteban-Torres, Bottacini, Woznicki, Hughes, Melgar, Ventura, Van Sinderen, Rossini and Nally. FAU - Hickey, Ana AU - Hickey A AD - APC Microbiome Ireland, University College Cork, Cork, Ireland. AD - School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland. FAU - Stamou, Panagiota AU - Stamou P AD - APC Microbiome Ireland, University College Cork, Cork, Ireland. FAU - Udayan, Sreeram AU - Udayan S AD - APC Microbiome Ireland, University College Cork, Cork, Ireland. AD - School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland. FAU - Ramon-Vazquez, Ana AU - Ramon-Vazquez A AD - APC Microbiome Ireland, University College Cork, Cork, Ireland. FAU - Esteban-Torres, Maria AU - Esteban-Torres M AD - APC Microbiome Ireland, University College Cork, Cork, Ireland. AD - School of Microbiology, University College Cork, Cork, Ireland. FAU - Bottacini, Francesca AU - Bottacini F AD - APC Microbiome Ireland, University College Cork, Cork, Ireland. AD - School of Microbiology, University College Cork, Cork, Ireland. FAU - Woznicki, Jerzy Adam AU - Woznicki JA AD - APC Microbiome Ireland, University College Cork, Cork, Ireland. FAU - Hughes, Owen AU - Hughes O AD - Luminex Corporation, Austin, TX, United States. FAU - Melgar, Silvia AU - Melgar S AD - APC Microbiome Ireland, University College Cork, Cork, Ireland. FAU - Ventura, Marco AU - Ventura M AD - Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy. FAU - Van Sinderen, Douwe AU - Van Sinderen D AD - APC Microbiome Ireland, University College Cork, Cork, Ireland. AD - School of Microbiology, University College Cork, Cork, Ireland. FAU - Rossini, Valerio AU - Rossini V AD - APC Microbiome Ireland, University College Cork, Cork, Ireland. FAU - Nally, Ken AU - Nally K AD - APC Microbiome Ireland, University College Cork, Cork, Ireland. AD - School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland. LA - eng PT - Journal Article DEP - 20210616 PL - Switzerland TA - Front Microbiol JT - Frontiers in microbiology JID - 101548977 PMC - PMC8242212 OTO - NOTNLM OT - Bifidobacterium breve OT - antigen presentation OT - dendritic cells OT - exopolysaccharides OT - host immune responses OT - macrophages COIS- OH is employed by the company Luminex Corporation which manufactures the Amnis ImageStream flow cytometer used in this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/07/06 06:00 MHDA- 2021/07/06 06:01 PMCR- 2021/06/16 CRDT- 2021/07/05 10:00 PHST- 2021/01/14 00:00 [received] PHST- 2021/05/11 00:00 [accepted] PHST- 2021/07/05 10:00 [entrez] PHST- 2021/07/06 06:00 [pubmed] PHST- 2021/07/06 06:01 [medline] PHST- 2021/06/16 00:00 [pmc-release] AID - 10.3389/fmicb.2021.653587 [doi] PST - epublish SO - Front Microbiol. 2021 Jun 16;12:653587. doi: 10.3389/fmicb.2021.653587. eCollection 2021.