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.

2.50
Hdl Handle:
http://hdl.handle.net/10033/317347
Title:
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.
Authors:
Blankenhaus, Birte; Reitz, Martina; Brenz, Yannick; Eschbach, Marie-Luise; Hartmann, Wiebke; Haben, Irma; Sparwasser, Tim ( 0000-0001-5645-902X ) ; Huehn, Jochen; Kühl, Anja; Feyerabend, Thorsten B; Rodewald, Hans-Reimer; Breloer, Minka
Abstract:
Accumulating 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.
Affiliation:
nstitute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research
Citation:
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. 2014, 10 (2):e1003913 PLoS Pathog.
Journal:
PLoS pathogens
Issue Date:
Feb-2014
URI:
http://hdl.handle.net/10033/317347
DOI:
10.1371/journal.ppat.1003913
PubMed ID:
24516385
Type:
Article
Language:
en
ISSN:
1553-7374
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorBlankenhaus, Birteen
dc.contributor.authorReitz, Martinaen
dc.contributor.authorBrenz, Yannicken
dc.contributor.authorEschbach, Marie-Luiseen
dc.contributor.authorHartmann, Wiebkeen
dc.contributor.authorHaben, Irmaen
dc.contributor.authorSparwasser, Timen
dc.contributor.authorHuehn, Jochenen
dc.contributor.authorKühl, Anjaen
dc.contributor.authorFeyerabend, Thorsten Ben
dc.contributor.authorRodewald, Hans-Reimeren
dc.contributor.authorBreloer, Minkaen
dc.date.accessioned2014-05-23T09:54:11Zen
dc.date.available2014-05-23T09:54:11Zen
dc.date.issued2014-02en
dc.identifier.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.en
dc.identifier.issn1553-7374en
dc.identifier.pmid24516385en
dc.identifier.doi10.1371/journal.ppat.1003913en
dc.identifier.urihttp://hdl.handle.net/10033/317347en
dc.description.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.en
dc.language.isoenen
dc.rightsArchived with thanks to PLoS pathogensen
dc.titleFoxp3⁺ 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.en
dc.typeArticleen
dc.contributor.departmentnstitute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Researchen
dc.identifier.journalPLoS pathogensen

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