乳腺局部天然免疫是奶牛乳腺抵抗微生物感染的第一道防线，乳腺局部免疫稳态失衡是引起乳房炎的重要原因。牛白血病病毒（BLV）在我国广泛流行，主要侵染淋巴细胞和单核细胞，可引起患牛免疫系统功能下降。BLV感染后，多数患牛临床症状不明显或呈长期潜伏感染状态，致使BLV在奶牛养殖中未被充分重视。研究表明，BLV可经血液/淋巴系统下行感染乳腺组织（71.4%，21/28），乳房炎患牛血液中BLV载量显著高于健康奶牛。我们推测BLV下行感染可能引起乳腺局部免疫稳态失衡，进而影响乳房炎的发生发展。因此，本项目拟运用流式细胞术、激光捕获显微切割、器官芯片等研究方法，从分子、细胞、微器官、组织、个体和群体六个层次，完整刻画BLV下行感染时奶牛乳腺天然免疫特征图谱，明确BLV重塑乳腺局部免疫微环境的作用途径，以期系统揭示BLV下行感染与奶牛乳房炎的内在联系，为破解奶牛乳房炎防控技术瓶颈提供突破口。

Innate immune function in mammary gland is essential for dairy cow defense against intramammary infection. Loss of immune homeostasis in mammary gland is the main reason for mastitis. Bovine leukemia virus (BLV) infection is widespread in China. A growing body of evidence supports that BLV disrupts normal immune functioning of lymphocytes and monocytes. Kakinuma et al. (2014) found that cows developed mastitis had higher peripheral blood BLV than cows without mastitis. In addition, Buehring et al. (1994) found that BLV is capable of infecting and expressing antigen in dairy cows’ glandular epithelium in vivo (71.4%, 21/28). We hypothesize that persistent mammary infection by BLV may disturb the immune homeostasis and increase the incidence of mastitis in dairy cow. However, the majority of producers do not actively try to manage or reduce BLV incidence within their herds. It is essential to explore this risk more fully to best assess the relationship of BLV and mastitis. Therefore, this project will use flow cytometry, laser capture microdissection, and organ-on-a-chip technologies to characterize the innate immune response when BLV infecting the dairy cows’ mammary glandular epithelium at molecule, cell, tissue, organ, system, organism, and population levels. Then, we will examine the change of local immunologic microenvironment in mammary gland when BLV infecting so as to evaluate the the relationship of BLV and mastitis. It is our hopes that a better understanding of the complex interactions between BLV infection and mammary gland microenvironments should prove useful for the future control of intramammary infections.