Increased mucin production and goblet cell hyperplasia are common features o f parasitic and allergic disease in man and animals. A protective role for mucus has been suggested in gastro-intestinal parasitic infections in rodents. The mucus associated molecules intelectin (ITLN), resistin like molecule beta (RELMP) and beta galactoside alpha 2-3 sialyltransferase (SIAT4C) are upregulated in nematode infections known to induce a typical T helper cell type 2 (Th2) response in mice. In the present work, it was hypothesised that these three mucus-associated molecules were co-regulated by Th2 cytokines and that their upregulation was part o f a typical anti-parasite response in other species. Sheep were chosen as a model because o f the economic importance o f both respiratory and gastrointestinal tract parasitic infections in sheep.
Culture o f a human colonic carcimoma cell line with either interleukin 4 (IL-4) or 1L-13 confirmed the upregulation o f ITLN and RELMP in a Th2 environment but failed to show co-regulation with SIAT4C. O f the T hl or Th2 cytokines examined only IFNy was found to have a significant effect on expression o f SIAT4C transcript. ITLN transcript and protein were demonstrated in sheep tissue and furthermore three different ITLNs (sITLN l, sITLN2, sITLN3) which had a differential tissue distribution were cloned and sequenced. SIAT4C was shown to be widely expressed in sheep tissues and the full sequence was deduced from expressed sequence tags, and confirmed. There was no evidence o f expression o f RELMP in sheep tissues examined.
sITLN transcripts were shown to be upregulated in response to IL-4 in an ex vivosheep tracheal explant culture model whilst sheep (s) SIAT4C was significantly downregulated in the same model. However, despite differential regulation by IL-4 ex vivo, in a sheep model o f infection with the abomasal nematode, Teladorsagicicircumcmcta, known to induce a Th2 biased response, sITLN transcripts and protein and sSIAT4C transcript were upregulated in response to a challenge infection.
Furthermore, slTLNl and sITLN2 were shown to upregulate at an earlier time point post challenge in previously infected (immune) compared to naive yearling sheep and lambs and significant upregulation o f sSIAT4C transcript was seen in previously infected challenged but not naive challenged sheep and lambs. In conclusion, whilst regulation o f sITLNs and sSIAT4C transcript expression in the mucosa may differ, these molecules may have an important role to play in the mucosal immune response to parasitic infections in sheep.