Foxp3⁺ regulatory T cells delay expulsion of intestinal nematodes by suppression of IL-9-driven mast cell activation in BALB/c but not in C57BL/6 mice.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Feyerabend, Thorsten B
MetadataShow full item record
AbstractAccumulating evidence suggests that IL-9-mediated immunity plays a fundamental role in control of intestinal nematode infection. Here we report a different impact of Foxp3⁺ regulatory T cells (Treg) in nematode-induced evasion of IL-9-mediated immunity in BALB/c and C57BL/6 mice. Infection with Strongyloides ratti induced Treg expansion with similar kinetics and phenotype in both strains. Strikingly, Treg depletion reduced parasite burden selectively in BALB/c but not in C57BL/6 mice. Treg function was apparent in both strains as Treg depletion increased nematode-specific humoral and cellular Th2 response in BALB/c and C57BL/6 mice to the same extent. Improved resistance in Treg-depleted BALB/c mice was accompanied by increased production of IL-9 and accelerated degranulation of mast cells. In contrast, IL-9 production was not significantly elevated and kinetics of mast cell degranulation were unaffected by Treg depletion in C57BL/6 mice. By in vivo neutralization, we demonstrate that increased IL-9 production during the first days of infection caused accelerated mast cell degranulation and rapid expulsion of S. ratti adults from the small intestine of Treg-depleted BALB/c mice. In genetically mast cell-deficient (Cpa3-Cre) BALB/c mice, Treg depletion still resulted in increased IL-9 production but resistance to S. ratti infection was lost, suggesting that IL-9-driven mast cell activation mediated accelerated expulsion of S. ratti in Treg-depleted BALB/c mice. This IL-9-driven mast cell degranulation is a central mechanism of S. ratti expulsion in both, BALB/c and C57BL/6 mice, because IL-9 injection reduced and IL-9 neutralization increased parasite burden in the presence of Treg in both strains. Therefore our results suggest that Foxp3⁺ Treg suppress sufficient IL-9 production for subsequent mast cell degranulation during S. ratti infection in a non-redundant manner in BALB/c mice, whereas additional regulatory pathways are functional in Treg-depleted C57BL/6 mice.
CitationFoxp3⁺ regulatory T cells delay expulsion of intestinal nematodes by suppression of IL-9-driven mast cell activation in BALB/c but not in C57BL/6 mice. 2014, 10 (2):e1003913 PLoS Pathog.
Affiliationnstitute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research
The following license files are associated with this item:
- Strongyloides ratti infection induces expansion of Foxp3+ regulatory T cells that interfere with immune response and parasite clearance in BALB/c mice.
- Authors: Blankenhaus B, Klemm U, Eschbach ML, Sparwasser T, Huehn J, Kühl AA, Loddenkemper C, Jacobs T, Breloer M
- Issue date: 2011 Apr 1
- Interleukin-9 promotes early mast cell-mediated expulsion of Strongyloides ratti but is dispensable for generation of protective memory.
- Authors: Reitz M, Hartmann W, Rüdiger N, Orinska Z, Brunn ML, Breloer M
- Issue date: 2018 Jun 5
- Basophils are dispensable for the establishment of protective adaptive immunity against primary and challenge infection with the intestinal helminth parasite Strongyloides ratti.
- Authors: Reitz M, Brunn ML, Voehringer D, Breloer M
- Issue date: 2018 Nov
- Mucosal mast cells are indispensable for the timely termination of Strongyloides ratti infection.
- Authors: Reitz M, Brunn ML, Rodewald HR, Feyerabend TB, Roers A, Dudeck A, Voehringer D, Jönsson F, Kühl AA, Breloer M
- Issue date: 2017 Mar
- Strongyloides ratti: implication of mast cell-mediated expulsion through FcepsilonRI-independent mechanisms.
- Authors: Watanabe K, Kishihara K, Hamano S, Koga M, Nomoto K, Tada I
- Issue date: 2009 Sep