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

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. © 2014 blankenhaus et al.