Low-level regulatory T-cell activity is essential for functional type-2 effector immunity to expel gastrointestinal helminths.

2.50
Hdl Handle:
http://hdl.handle.net/10033/607409
Title:
Low-level regulatory T-cell activity is essential for functional type-2 effector immunity to expel gastrointestinal helminths.
Authors:
Smith, K A; Filbey, K J; Reynolds, L A; Hewitson, J P; Harcus, Y; Boon, L; Sparwasser, Tim ( 0000-0001-5645-902X ) ; Hämmerling, G; Maizels, R M
Abstract:
Helminth infection is frequently associated with the expansion of regulatory T cells (Tregs) and suppression of immune responses to bystander antigens. We show that infection of mice with the chronic gastrointestinal helminth Heligmosomoides polygyrus drives rapid polyclonal expansion of Foxp3(+)Helios(+)CD4(+) thymic (t)Tregs in the lamina propria and mesenteric lymph nodes while Foxp3(+)Helios(-)CD4(+) peripheral (p)Treg expand more slowly. Notably, in partially resistant BALB/c mice parasite survival positively correlates with Foxp3(+)Helios(+)CD4(+) tTreg numbers. Boosting of Foxp3(+)Helios(+)CD4(+) tTreg populations by administration of recombinant interleukin-2 (rIL-2):anti-IL-2 (IL-2C) complex increased worm persistence by diminishing type-2 responsiveness in vivo, including suppression of alternatively activated macrophage and granulomatous responses at the sites of infection. IL-2C also increased innate lymphoid cell (ILC) numbers, indicating that Treg functions dominate over ILC effects in this setting. Surprisingly, complete removal of Tregs in transgenic Foxp3-DTR mice also resulted in increased worm burdens, with "immunological chaos" evident in high levels of the pro-inflammatory cytokines IL-6 and interferon-γ. In contrast, worm clearance could be induced by anti-CD25 antibody-mediated partial depletion of early Treg, alongside increased T helper type 2 responses and without incurring pathology. These findings highlight the overarching importance of the early Treg response to infection and the non-linear association between inflammation and the prevailing Treg frequency.
Affiliation:
Twincore Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hanover and the Helmholtz Centre for Infection Research, Hanover, Germany.
Citation:
Low-level regulatory T-cell activity is essential for functional type-2 effector immunity to expel gastrointestinal helminths. 2016, 9 (2):428-43 Mucosal Immunol
Journal:
Mucosal immunology
Issue Date:
Mar-2016
URI:
http://hdl.handle.net/10033/607409
DOI:
10.1038/mi.2015.73
PubMed ID:
26286232
Type:
Article
Language:
en
ISSN:
1935-3456
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorSmith, K Aen
dc.contributor.authorFilbey, K Jen
dc.contributor.authorReynolds, L Aen
dc.contributor.authorHewitson, J Pen
dc.contributor.authorHarcus, Yen
dc.contributor.authorBoon, Len
dc.contributor.authorSparwasser, Timen
dc.contributor.authorHämmerling, Gen
dc.contributor.authorMaizels, R Men
dc.date.accessioned2016-04-29T08:54:36Zen
dc.date.available2016-04-29T08:54:36Zen
dc.date.issued2016-03en
dc.identifier.citationLow-level regulatory T-cell activity is essential for functional type-2 effector immunity to expel gastrointestinal helminths. 2016, 9 (2):428-43 Mucosal Immunolen
dc.identifier.issn1935-3456en
dc.identifier.pmid26286232en
dc.identifier.doi10.1038/mi.2015.73en
dc.identifier.urihttp://hdl.handle.net/10033/607409en
dc.description.abstractHelminth infection is frequently associated with the expansion of regulatory T cells (Tregs) and suppression of immune responses to bystander antigens. We show that infection of mice with the chronic gastrointestinal helminth Heligmosomoides polygyrus drives rapid polyclonal expansion of Foxp3(+)Helios(+)CD4(+) thymic (t)Tregs in the lamina propria and mesenteric lymph nodes while Foxp3(+)Helios(-)CD4(+) peripheral (p)Treg expand more slowly. Notably, in partially resistant BALB/c mice parasite survival positively correlates with Foxp3(+)Helios(+)CD4(+) tTreg numbers. Boosting of Foxp3(+)Helios(+)CD4(+) tTreg populations by administration of recombinant interleukin-2 (rIL-2):anti-IL-2 (IL-2C) complex increased worm persistence by diminishing type-2 responsiveness in vivo, including suppression of alternatively activated macrophage and granulomatous responses at the sites of infection. IL-2C also increased innate lymphoid cell (ILC) numbers, indicating that Treg functions dominate over ILC effects in this setting. Surprisingly, complete removal of Tregs in transgenic Foxp3-DTR mice also resulted in increased worm burdens, with "immunological chaos" evident in high levels of the pro-inflammatory cytokines IL-6 and interferon-γ. In contrast, worm clearance could be induced by anti-CD25 antibody-mediated partial depletion of early Treg, alongside increased T helper type 2 responses and without incurring pathology. These findings highlight the overarching importance of the early Treg response to infection and the non-linear association between inflammation and the prevailing Treg frequency.en
dc.language.isoenen
dc.titleLow-level regulatory T-cell activity is essential for functional type-2 effector immunity to expel gastrointestinal helminths.en
dc.typeArticleen
dc.contributor.departmentTwincore Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hanover and the Helmholtz Centre for Infection Research, Hanover, Germany.en
dc.identifier.journalMucosal immunologyen

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in HZI are protected by copyright, with all rights reserved, unless otherwise indicated.