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Impaired interleukin‐4 signalling promotes establishment of Haemonchus contortus in sheep
Author(s) -
Jacobs Jesica R.,
Greiner Scott P.,
Bowdridge Scott A.
Publication year - 2018
Publication title -
parasite immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 75
eISSN - 1365-3024
pISSN - 0141-9838
DOI - 10.1111/pim.12597
Subject(s) - haemonchus contortus , biology , peripheral blood mononuclear cell , downregulation and upregulation , immunology , immune system , interleukin 4 , interleukin 10 , gene expression , gene , helminths , genetics , in vitro
Summary Reduced worm burden in St. Croix (STC) sheep during Haemonchus contortus (Hc) infection is predicated on rapid interleukin‐4 (IL‐4) signalling and T helper type 2 immune (Th2) response. The aim of these studies was to further elucidate differences in Th2 responses by STC and Suffolk (SUF) sheep. Ten days after challenge Hc infection, peripheral blood mononuclear cells (PBMC) were collected and cultured with larval (HcLA) and adult worm (HcWA) antigen. STC PBMC produced nearly twice as much IL‐4 as SUF (823.57 pg/mL vs 454.28 pg/mL) at 6 hours of HcLA culture despite no difference in IL‐4 gene expression and the IL‐4 receptor ( IL4R α) was upregulated in STC PBMC but was undetectable in SUF. Expression of other Th2‐type genes were increased in STC PBMC including IL13 , IL5 and MRC1 . IL‐4 supplementation to HcLA culture was insufficient to achieve upregulation of Th2 genes in SUF PBMC. Production of IL‐4 did not occur in SUF PBMC until 24 hours after culture with HcLA, and expression of IL4 in the abomasum was similarly delayed until 10 days after challenge infection, which was associated with significantly higher larval burden (530 vs 16). These data demonstrate delayed upregulation of Th2 genes in SUF sheep contributes to susceptibility to Hc.