Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 46, Issue 5, Pages 1180-1192Publisher
WILEY-BLACKWELL
DOI: 10.1002/eji.201545905
Keywords
Anergy; C-type lectin receptors; Dendritic cells; Helminth infection; Host-pathogen interactions; Mannose receptor; T-cell responses
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Funding
- Science Foundation, Ireland, Basic Project Grant [11/RFP.1/BIC/3109]
- Science Foundation Ireland (SFI) [11/RFP.1/BIC/3109] Funding Source: Science Foundation Ireland (SFI)
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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.
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