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.
| 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. |
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| Authors: | Birte Blankenhaus, Martina Reitz, Yannick Brenz, Marie-Luise Eschbach, Wiebke Hartmann, Irma Haben, Tim Sparwasser, Jochen Huehn, Anja Kühl, Thorsten B Feyerabend, Hans-Reimer Rodewald, Minka Breloer |
| Source: | PLoS Pathogens, Vol 10, Iss 2, p e1003913 (2014) |
| Publisher Information: | Public Library of Science (PLoS), 2014. |
| Publication Year: | 2014 |
| Collection: | LCC:Immunologic diseases. Allergy LCC:Biology (General) |
| Subject Terms: | Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5 |
| More Details: | 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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1553-7366 1553-7374 |
| Relation: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24516385/pdf/?tool=EBI; https://doaj.org/toc/1553-7366; https://doaj.org/toc/1553-7374 |
| DOI: | 10.1371/journal.ppat.1003913 |
| Access URL: | https://doaj.org/article/4ddcecfed62d41c3b6fb6b10b9d31484 |
| Accession Number: | edsdoj.4ddcecfed62d41c3b6fb6b10b9d31484 |
| Database: | Directory of Open Access Journals |
| ISSN: | 15537366 15537374 |
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| DOI: | 10.1371/journal.ppat.1003913 |
| Published in: | PLoS Pathogens |
| Language: | English |