Thymic stromal lymphopoietin contributes to protection of mice from Strongyloides venezuelensis infection by CD4+ T cell-dependent and -independent pathways

Abstract

When animals are infected with helminthic parasites, resistant hosts mount type II helper T (Th2) immune responses to expel worms. Recent studies have clearly shown that epithelial cell-derived cytokines contribute to the induction of Th2 immune responses. Here we demonstrate the role of endogenous thymic stromal lymphopoietin (TSLP) for protection against Strongyloides venezuelensis (S. venezuelensis) infection, utilizing TSLP receptor-deficient Crlf2^-/- mice. The number of eggs per gram of feces (EPG) and worm burden were significantly higher in Crlf2^-/- mice than in wild type (WT) mice. S. venezuelensis infection induced Tslp mRNA expression in the skin, lung, and intestine and also facilitated the accumulation of mast cells in the intestine in a TSLP-dependent manner. Furthermore, CD4⁺ T cells from S. venezuelensis-infected Crlf2^-/- mice showed diminished capacity to produce Th2 cytokines in the early stage of infection. Finally, CD4⁺ cell-depleted Crlf2^-/- mice still showed higher EPG counts and worm burden than CD4⁺ cell-depleted WT mice, indicating that TSLP contributes to protecting mice against S. venezuelensis infection in both CD4⁺ T cell-dependent and -independent manners.

Keywords: Epithelial cell-derived cytokines; Intestinal nematode; Mast cells; Th2; Thymic stromal lymphopoietin receptor.