Diabetes-prone NOD mice are resistant to Mycobacterium avium and the infection prevents autoimmune disease
Diabetes-prone NOD mice are resistant to Mycobacterium avium and the infection prevents autoimmune disease
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DOI：
10.1046/j.1365-2567.1996.d01-717.x
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发表时间：
1996-09-01
期刊：
影响因子：
6.4
通讯作者：
Aguas, AP
中科院分区：
文献类型：
--
作者：
Bras, A;Aguas, AP
最近提出，非肥胖糖尿病（NOD）小鼠的糖尿病基因与Beg基因相关，该基因与对分枝杆菌感染的抗性相关;然而，尚未确定NOD小鼠是否对感染具有抗性或易感性，尽管先前有关于NOD小鼠对其他细胞内寄生虫的反应的研究（例如Kaye et al.毛皮22：357-364）。我们在这里研究了这个问题，以及分枝杆菌感染对小鼠糖尿病自然史的影响。雌性NOD小鼠在2月龄时，即在小鼠显示糖尿病之前，用10（8）种活的鸟分枝杆菌（Mycobacterium avium）杆菌腹膜内感染;研究它们直到6月龄（当超过一半的未处理的雌性NOD小鼠显示糖尿时）。为了确定NOD小鼠是否对M.本研究比较了小鼠肝、脾中细菌生长的动力学与M.禽流感易感（BALB/c）和抗性（C3 H）小鼠品系。NOD小鼠能够控制M.禽流感病毒感染，遵循类似于在感染的C3 H小鼠中观察到的模式。分枝杆菌感染阻止了所有感染的NOD小鼠中糖尿病的表达，并且还降低了治疗小鼠中蛋白尿的发生率。感染的NOD小鼠表现出显着的增强抗体对65 000分枝杆菌抗原（热休克蛋白（HSP）65）的感染的第二个月，这些升高的滴度缓慢下降，在接下来的几个月，抗HSP 65抗体未检测到年龄匹配的控制。这是NOD小鼠对分枝杆菌感染具有天然抵抗力的首次证明，我们进一步证实了由分枝杆菌及其HSP 65抗原引发的免疫应答在NOD小鼠预防糖尿病中的作用。
It was recently proposed that the diabetes genes of non-obese diabetic (NOD) mice are linked to the Beg gene that is associated with resistance to infection by mycobacteria; however, it has not been established whether NOD mice are resistant or susceptible to the infection, although there are previous investigations on response of NOD mice to other intracellular parasites (e.g. Kaye et al., fur. J. Immunol. 22: 357-364). We have investigated here this question, as well as the consequences of mycobacterial infection on the natural history of murine diabetes. Female NOD mice were intraperitoneally infected with 10(8) viable bacilli of Mycobacterium avium at 2 months of age, i.e. before the mice show diabetes; they were studied up to the sixth month of age (when more than half of untreated female NOD mice show glycosuria). To determine whether NOD mice were susceptible or resistant to M. avium infection, we have compared the kinetics of bacterial growths in liver and spleen of the mice with those determined in M. avium-susceptible (BALB/c) and resistant (C3H) strains of mice. NOD mice were able to control the M. avium infection, following a pattern similar to that observed in infected C3H mice. The mycobacterial infection prevented the expression of diabetes in all of the infected NOD mice and it also decreased the incidence of proteinuria in the treated mice. The infected NOD mice showed a marked enhancement in antibodies against the 65 000 mycobacterial antigen (heal-shock protein (hsp) 65) up to the second month of infection and these elevated titres slowly decreased in the following months; anti-hsp 65 antibodies were not detected in age-matched controls. This is the first demonstration that NOD mice are naturally resistant to mycobacterial infection, and we reinforce evidence on the role of immune response triggered by mycobacteria and its hsp 65 antigen in prevention of diabetes in NOD mice.