Cheville N F, Kunkle R A, Jensen A E, Palmer M V
Brucellosis Research Unit, National Animal Disease Center, U.S.D.A., Ames, Iowa, USA.
Lab Invest. 1995 Jul;73(1):96-102.
Brucella abortus is sequestered in lymphoid tissues, bone, and liver during chronic asymptomatic brucellosis of cattle and humans. The sites of cellular infection, cytopathology of infected cells, and mechanisms of bacterial recrudescence have not been identified. A laboratory model is needed for the study of chronic brucellosis.
Livers of athymic and euthymic mice infected with virulent B. abortus were cultured and examined morphologically to determine the effects of T cell dysfunction on persistence of intracellular bacteria. Bacterial Ag was detected immunohistochemically and by ultrastructural immunogold techniques.
Bacteria in livers of euthymic mice rose to high titers at postinoculation Day (PID) 6 but rapidly declined and were slowly cleared. In athymic mice, bacteria did not reach such high titers and persisted in all mice to PID 121. Granulomas were similar in size, structure, and number in both groups of mice through PID 28. Thereafter, euthymic mice developed many granulomas that disappeared by PID 121. In contrast, athymic mice failed to maintain granuloma formation but had diffuse lymphohistiocytic pericholangiitis with brucella Ag in subepithelial stellate cells, intraepithelial monocytes, and luminal macrophages. Intact bacteria were identified in lysosomes of macrophages and neutrophils only in acute infection.
Athymic mice have normal or enhanced resistance to B. abortus in the first 10 days of infection but fail to maintain granuloma formation, do not clear brucellae from the liver, and develop persistent infection of the biliary tract. Brucellar Ag persists in chronically infected livers in periductal inflammatory tissues.
在牛和人的慢性无症状布鲁氏菌病期间，流产布鲁氏菌隐匿于淋巴组织、骨骼和肝脏中。细胞感染部位、受感染细胞的细胞病理学以及细菌复发机制尚未明确。慢性布鲁氏菌病的研究需要一个实验室模型。
对感染强毒流产布鲁氏菌的无胸腺小鼠和有胸腺小鼠的肝脏进行培养，并进行形态学检查，以确定T细胞功能障碍对细胞内细菌持续存在的影响。通过免疫组织化学和超微结构免疫金技术检测细菌抗原。
有胸腺小鼠肝脏中的细菌在接种后第6天（PID 6）升至高滴度，但迅速下降并缓慢清除。在无胸腺小鼠中，细菌未达到如此高的滴度，并在所有小鼠中持续至PID 121。两组小鼠在PID 28之前肉芽肿的大小、结构和数量相似。此后，有胸腺小鼠出现许多肉芽肿，到PID 121时消失。相比之下，无胸腺小鼠未能维持肉芽肿形成，但有弥漫性淋巴细胞性胆管周围炎，在皮下星状细胞、上皮内单核细胞和管腔内巨噬细胞中有布鲁氏菌抗原。仅在急性感染时，在巨噬细胞和中性粒细胞的溶酶体中发现完整细菌。
无胸腺小鼠在感染的前10天对流产布鲁氏菌具有正常或增强的抵抗力，但未能维持肉芽肿形成，未从肝脏清除布鲁氏菌，并发展为胆道持续感染。布鲁氏菌抗原在慢性感染肝脏的导管周围炎症组织中持续存在。
