Simple SummarySkin lesions in cattle associated with feeding byHaematobiafly species are a significant health issue in northern Australian cattle. These lesions have most commonly been attributed to the effects ofStephanofilarianematodes vectored by theHaematobiaspp. flies. However, the exact etiology of these lesions and reasons for the variation between the cattle in the severity of lesions was unclear. This study investigated the cutaneous responses to fly and nematode antigens in lesion-resistant and susceptible cattle, which indicated that differences in the hypersensitivity response to buffalo fly (Haematobia irritans exigua) antigens is a key factor underlying the variation amongst the cattle in susceptibility-to-lesion development. There was no association found between the intensity of fly infestation and lesion susceptibility. The findings from this study suggest that further characterization of the skin response could lead to the identification of the biomarkers for selecting cattle with an increased resistance to buffalo fly lesion development.AbstractThis study investigated the role of cattle immune responses in the pathogenesis of buffalo fly (Haematobia irritans exigua) (BF) lesions. Brangus steers phenotyped for lesion development were divided into three groups: high lesion susceptibility (HL), low lesion susceptibility (LL) and no lesions (NL), based on lesion severity scores. Each steer was injected intradermally with different concentrations of BF,Onchocerca gibsoni(Og), andMusca domestica(Md) antigens. At 1 h post-injection, wheal areas at BF injection sites were found to be significantly larger in HL than NL cattle, but there were no significant differences (p< 0.05) found between either the HL or NL cattle and LL cattle. At 24, 48, and 72 h post-injection, the skinfold thickness response to both BF and Md antigens was significantly greater in the HL group than the NL group. However, skin thickness was significantly greater for the BF antigens than the Md antigens (p< 0.05). There were no significant differences found between the LL and NL animals in response to the BF antigens at any time, and no significant differences were determined between any of the lesion groups in response to the Og antigens. Histological examination of skin sections taken from the BF antigen injection sites in HL cattle at 72 h post-injection revealed necrosis of the epidermis and superficial dermis, along with severe eosinophilic inflammation. This study suggests that differences in the hypersensitivity to BF antigens underlie differences amongst the cattle in their susceptibility to the development of BF lesions, and breeding for immune-related biomarkers may assist in selecting more BF lesion-resistant cattle.