Innate Immune Responses Associated with Resistance againstHaemonchus contortusin Morada Nova Sheep

The immune response againstHaemonchus contortusinfections is primarily associated with the Th2 profile. However, the exact mechanisms associated with increased sheep resistance against this parasite remains poorly elucidated. The present study is aimed at evaluating mediators from the innate immune response in lambs of the Morada Nova Brazilian breed with contrastingH.contortusresistance phenotypes. Briefly, 287 lambs were characterized through fecal egg counts (FEC) and packed cell volume (PCV) after two independent experimental parasitic challenges with 4,000 H.contortusL3. 20 extreme resistance phenotypes (10 most resistant and 10 most susceptible) were selected, subjected to a third artificial infection with 4,000 L3, and euthanized 7 days later. Tissue samples were collected from abomasal fundic and pyloric mucosa and abomasal lymph nodes. Blood samples were collected at days 0 and 7 of the third parasitic challenge. RNA was extracted from tissue and blood samples for relative quantification of innate immune-related genes by RT-qPCR. For the abomasal fundic mucosa, increasedTNFαandIL1βexpression levels ( P<0.05 ) were found in the susceptible animals, while resistant animals hadIL33superiorly expressed ( P<0.05 ). Higher levels ( P<0.05 ) ofTLR2andCFIwere found in the abomasal pyloric mucosa of resistant animals.TNFαwas at higher levels ( P<0.05 ) in the blood of susceptible lambs, at day 0 of the third artificial infection. The exacerbated proinflammatory response observed in susceptible animals, at both local and systemic levels, may be a consequence of highH.contortusparasitism. This hypothesis is corroborated by the higher blood levels ofTNFαbefore the onset of infection, which probably remained elevated from the previous parasitic challenges. On the other hand, resistant lambs had an enhanced response mediated by TLR recognition and complement activation. Nevertheless, this is the first study to directly associate sheep parasitic resistance with IL33, an innate trigger of the Th2-polarized response.