Waters W R, Rahner T E, Palmer M V, Cheng D, Nonnecke B J, Whipple D L
Bacterial Diseases of Livestock Research Unit, National Animal Disease Center, USDA Agricultural Research Service, Ames, Iowa 50010, USA.
Infect Immun. 2003 Jan;71(1):317-26. doi: 10.1128/IAI.71.1.317-326.2003.
Mycobacterium bovis infection of cattle represents a natural host-pathogen interaction and, in addition to its economic and zoonotic impact, represents a model for human tuberculosis. Extravasation and trafficking of activated lymphocytes to inflammatory sites is modulated by differential expression of multiple surface adhesion molecules. However, effects of M. bovis infection on adhesion molecule expression have not been characterized. To determine these changes, peripheral blood mononuclear cells from M. bovis-infected cattle were stimulated with M. bovis purified protein derivative (PPD) or pokeweed mitogen (PWM) and evaluated concurrently for proliferation and activation marker expression. Stimulation with PPD or PWM increased CD25 and CD44 mean fluorescence intensity (MFI) and decreased CD62L MFI on CD4(+) cells from infected animals. CD62L MFI on PPD- and PWM-stimulated gammadelta T-cell receptor-positive (TCR(+)) and CD8(+) cells was also reduced compared to that of nonstimulated gammadelta TCR(+) and CD8(+) cells. Using a flow cytometry-based proliferation assay, it was determined that proliferating cells, regardless of lymphocyte subset, exhibited increased expression of CD25 and CD44 and decreased expression of CD62L compared to cells that had not proliferated. In contrast to proliferation, activation-induced apoptosis of CD4(+) cells resulted in a significant down regulation of CD44 expression. Lymphocytes obtained from lungs of M. bovis-infected cattle also had reduced expression of CD44 compared to lymphocytes from lungs of noninfected cattle. These alterations in surface molecule expression upon activation likely impact trafficking to sites of inflammation and the functional capacity of these cells within tuberculous granulomas.
牛分枝杆菌感染牛代表了一种自然宿主 - 病原体相互作用,除了其经济影响和人畜共患病影响外,还代表了人类结核病的一个模型。活化淋巴细胞向炎症部位的外渗和运输受多种表面粘附分子差异表达的调节。然而,牛分枝杆菌感染对粘附分子表达的影响尚未得到表征。为了确定这些变化,用牛分枝杆菌纯化蛋白衍生物(PPD)或商陆丝裂原(PWM)刺激来自感染牛分枝杆菌的牛的外周血单核细胞,并同时评估其增殖和活化标志物表达。用PPD或PWM刺激会增加感染动物CD4(+)细胞上CD25和CD44的平均荧光强度(MFI),并降低CD62L MFI。与未刺激的γδT细胞受体阳性(TCR(+))和CD8(+)细胞相比,PPD和PWM刺激的γδTCR(+)和CD8(+)细胞上的CD62L MFI也降低。使用基于流式细胞术的增殖测定法确定,与未增殖的细胞相比,无论淋巴细胞亚群如何,增殖细胞均表现出CD25和CD44表达增加以及CD62L表达降低。与增殖相反,CD4(+)细胞的活化诱导凋亡导致CD44表达显著下调。与未感染牛肺部的淋巴细胞相比,从感染牛分枝杆菌的牛肺部获得的淋巴细胞中CD44的表达也降低。活化后这些表面分子表达的改变可能会影响向炎症部位的运输以及这些细胞在结核性肉芽肿内的功能能力。