Local cytokine transcription in naïve and previously infected sheep and lambs following challenge with Teladorsagia circumcincta.

BACKGROUND: The abomasal helminth Teladorsagia circumcincta is one of the most economically important parasites affecting sheep in temperate regions. Infection is particularly detrimental to lambs, in which it can cause pronounced morbidity and severe production losses. Due to the spreading resistance of this parasite to all classes of anthelmintic drugs, teladorsagiosis is having an increasingly severe impact on the sheep industry with significant implications for sheep welfare. Protective immunity develops slowly, wanes rapidly and does not appear to be as effective in young lambs. To investigate the development of immunity to T. circumcincta in sheep and lambs, we used cytokine transcript profiling to examine differences in the abomasal mucosa and gastric lymph node of naïve and previously infected sheep and lambs following challenge. RESULTS: The results of these experiments demonstrated that the abomasal mucosa is a major source of cytokines during abomasal helminth infection. A local Th2-type cytokine response was observed in the abomasal mucosa and gastric lymph node of the previously infected sheep and lambs when compared with those of the naïve during the early stages of infection. In contrast, a pro-inflammatory component more was evident in the abomasal mucosa and gastric lymph node of the naïve sheep when compared with those of the previously infected, which was not observed in the lambs. CONCLUSIONS: The greater levels of Th2-type cytokine transcripts in both the abomasum and gastric lymph node of the previously infected compared with naïve sheep and lambs emphasises the importance of these mechanisms in the immune response to T. circumcincta infection. Younger lambs appear to be able to generate similar Th2-type responses in the abomasum suggesting that the increased morbidity and apparent lack of resistance in younger lambs following continuous or repeated exposure to T. circumcincta is unlikely to be due to a lack of appropriate Th2-type cytokine production.

Up-regulation of intelectin in sheep after infection with Teladorsagia circumcincta.

A novel intelectin molecule designated sheep intelectin 2 (sITLN2) was detected in sheep abomasal mucosa. The full sequence shared 76-83% homology with other mammalian intelectins. Intelectins are mucus-associated proteins that have been shown to be up-regulated in gastrointestinal nematode infections in rodents and in human asthma. Expression of sheep abomasal ITLN2 mRNA was significantly up-regulated on day 10 post-challenge of worm-free sheep with Teladorsagia circumcincta and at day 2 in previously infected, immune sheep. Increased expression of ITLN protein following challenge was confirmed by Western blot and was immunolocalised to the mucous neck cells of the abomasal mucosa. Infection with T. circumcincta was also associated with increased levels of abomasal transcripts encoding sheep mast cell protease-1, ovine galectin-14 and IL4, which collectively suggested a Th2 type response. Intelectin may play an important role in the mucosal response to gastrointestinal nematode infections in ruminants.