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© Research
Publication : The Journal of infectious diseases

Aspergillus fumigatus Cell Wall α-(1,3)-Glucan Stimulates Regulatory T-Cell Polarization by Inducing PD-L1 Expression on Human Dendritic Cells

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in The Journal of infectious diseases - 05 Dec 2017

Stephen-Victor E, Karnam A, Fontaine T, Beauvais A, Das M, Hegde P, Prakhar P, Holla S, Balaji KN, Kaveri SV, Latgé JP, Aimanianda V, Bayry J

Link to Pubmed [PMID] – 28968869

J. Infect. Dis. 2017 12;216(10):1281-1294

Background: Human dendritic cell (DC) response to α-(1,3)-glucan polysaccharide of Aspergillus fumigatus and ensuing CD4+ T-cell polarization are poorly characterized.

Methods: α-(1,3)-Glucan was isolated from A. fumigatus conidia and mycelia cell wall. For the analysis of polarization, DCs and autologous naive CD4+ T cells were cocultured. Phenotype of immune cells was analyzed by flow cytometry, and cytokines by enzyme-linked immunosorbent assay (ELISA). Blocking antibodies were used to dissect the role of Toll-like receptor 2 (TLR2) and programmed death-ligand 1 (PD-L1) in regulating α-(1,3)-glucan-mediated DC activation and T-cell responses. DCs from TLR2-deficient mice were additionally used to consolidate the findings.

Results: α-(1,3)-Glucan induced the maturation of DCs and was dependent in part on TLR2. “α-(1,3)-Glucan-educated” DCs stimulated the activation of naive T cells and polarized a subset of these cells into CD4+CD25+FoxP3+ regulatory T cells (Tregs). Mechanistically, Treg stimulation by α-(1,3)-glucan was dependent on the PD-L1 pathway that negatively regulated interferon-gamma (IFN-γ) secretion. Short α-(1,3)-oligosaccharides lacked the capacity to induce maturation of DCs but significantly blocked α-(1,3)-glucan-induced Treg polarization.

Conclusions: PD-L1 dictates the balance between Treg and IFN-γ responses induced by α-(1,3)-glucan. Our data provide a rationale for the exploitation of immunotherapeutic approaches that target PD-1-PD-L1 to enhance protective immune responses to A. fumigatus infections.

https://www.ncbi.nlm.nih.gov/pubmed/28968869