Characterization of local immune responses associated with the parasitic resistance phenotype in Morada Nova lambs

Considering the impact of Haemonchus contortus infection on sheep breeding, there is an increasing number of studies addressing host resistance against to this parasite, and the understanding of directly related immune mechanisms is essential. The response to helminth infections is predominantly Th2- polarized, although the immune mechanisms that confer resistance to sheep are not fully elucidated. The present study aimed to evaluate the local immune responses (abomasum) associated with resistance to H. contortus infection in Morada Nova lambs, a breed considered resistant. A 287 sheep flock was phenotyped, by means of fecal egg counts, packed cell volume and body weight, after two parasitic challenges with 4000 L3. The 20 extremes of infection (10 most resistant and 10 most susceptible) were submitted to a third challenge and slaughtered seven days later. 22 immune-related genes were quantified (RT-qPCR) in abomasum and abomasal lymph nodes. In addition, abomasal eosinophils and mast cells were quantified, and IgG and IgA levels were measured (ELISA) in abomasal mucus. Genes related to innate response (TLR2 and CFI) were superiorly expressed in the pyloric region of the resistant animals. IL33 (Th2 polarization promoter) and MS4A2 (IgE receptor) were also at higher levels in this group. Proinflammatory cytokines (TNFα and IL1β) were superiorly expressed in the fundic region of the susceptible group, which also had IL4 (Th2 response) superiorly expressed in their abomasal lymph nodes. Resistant lambs had higher eosinophils counts in abomasal fundic region, and higher levels of local IgA. As expected, susceptible animals had an exacerbated inflammatory response, whereas the resistant ones had a response mediated by eosinophils and IgE. In addition, the results evidenced importance of the innate response in sheep resistance against H. contortus infection, mediated by TLR2 and complement system. Nevertheless, this is the first study to directly associate the parasite resistance phenotype in production animals with higher levels of IL33. (AU)