title: Fasciola hepatica tegumental antigens induce anergic-like T cells via dendritic cells in a mannose receptor-dependent manner.
abstract: FoxP3(+) Treg cells and anergic T cells are the two regulatory phenotypes of T-cell responses associated with helminth infection. Here, we examine the T-cell responses in mice during Fasciola hepatica infection, and to its tegumental coat antigens (FhTeg) that are shed from the fluke every 2-3 h. FhTeg comprises a rich source of glycoproteins, mainly oligomannose N-glycans that bind to mannose receptor. This study demonstrated a novel mechanism for the T-cell unresponsiveness observed during F. hepatica infection and after injection with FhTeg. Markers of T-cell anergy, such as GRAIL, EGR2, ICOS, and ITCH, are enhanced amongst CD4(+) T-cell populations during infection and following FhTeg injection. This is characterized by a lack of cytokine responses and reduced proliferative activity, which can be reversed with the addition of IL-2. FhTeg-activated dendritic cells (DCs) suppress T cells in vitro as measured by enhanced GRAIL and CTLA4 by RNA and suppressed cytokine expression in anti-CD3 stimulated CD4(+) T cells. FhTeg-treated DCs have enhanced MR expression, which is critical for DC-CD4(+) T-cell communication. Taken together, this study presents markers of anergy in a mouse model of F. hepatica infection, and improves our understanding of host-pathogen interactions and how helminths modulate host immunity.
authors.affiliation: Fundamental and Translational Immunology Group, School of Biotechnology, Faculty of Science and Health, Dublin City University, Glasnevin, Dublin, Ireland.
authors.forename: Allison
authors.initials: A
authors.lastname: Aldridge
authors.affiliation: Fundamental and Translational Immunology Group, School of Biotechnology, Faculty of Science and Health, Dublin City University, Glasnevin, Dublin, Ireland.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: O'Neill
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D017635:Clonal Anergy; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D051767:Early Growth Response Protein 2 / Q000235:genetics; D005210:Fasciola hepatica / Q000737:chemistry / Q000276:immunology*; D054884:Host-Pathogen Interactions; D060889:Inducible T-Cell Co-Stimulator Protein / Q000235:genetics; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: D000947:Antigens, Helminth; D015415:Biomarkers; D016207:Cytokines; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; C471637:Itch protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: Anergy; C-type lectin receptors; Dendritic cells; Helminth infection; Host-pathogen interactions; Mannose receptor; T-cell responses