Watts Christopher J, Hahn Beth L, Sohnle Peter G
Division of Infectious Diseases, Department of Medicine, Medical College of Wisconsin, Consultant Care Division and Research Service, Milwaukee VA Medical Center, Milwaukee, USA.
J Infect Dis. 2009 Mar 1;199(5):673-9. doi: 10.1086/596631.
Previous studies in a murine cutaneous anthrax model have demonstrated that hairless and haired HRS/J mice are extremely resistant to Bacillus anthracis. Because these mice are relatively thymus deficient, we used C57BL/6 athymic nude and euthymic mice to evaluate the relationship between T cell deficiency and this heightened resistance.
Animals were epicutaneously inoculated with 1 X 10(7) B. anthracis (Sterne) spores onto abraded skin or injected with the spores intradermally or subcutaneously. The mice were then either monitored for survival or killed for quantitative histological experiments.
Athymic mice were found to be markedly resistant to all 3 inoculation routes, compared with euthymic C57BL/6 mice. Athymic mice rendered leukopenic with cyclophosphamide became susceptible. Histological examination demonstrated increased inflammation and absence of organisms in the skin of athymic mice, compared with euthymic ones. The numbers of organisms in the athymic animals increased markedly after cyclophosphamide treatment. Superficial exudate fluids of inoculated skin showed many more neutrophils and ingested bacilli in the athymic mice.
These experiments demonstrate that athymic nude C57BL/6 mice are markedly resistant to experimental cutaneous anthrax, apparently because of a superficial neutrophilic response that clears the inoculated organisms before they can invade the underlying skin.
先前在小鼠皮肤炭疽模型中的研究表明,无毛和有毛的HRS/J小鼠对炭疽杆菌具有极强的抵抗力。由于这些小鼠相对胸腺缺陷,我们使用C57BL/6无胸腺裸鼠和有胸腺小鼠来评估T细胞缺陷与这种增强的抵抗力之间的关系。
将动物在擦伤的皮肤上经皮接种1×10⁷炭疽芽孢杆菌(Sterne株)孢子,或进行皮内或皮下注射。然后监测小鼠的存活情况,或处死小鼠进行定量组织学实验。
与有胸腺的C57BL/6小鼠相比,发现无胸腺小鼠对所有3种接种途径均具有显著抗性。用环磷酰胺使无胸腺小鼠白细胞减少后,它们变得易感。组织学检查表明,与有胸腺小鼠相比,无胸腺小鼠皮肤中的炎症增加且无细菌。环磷酰胺治疗后,无胸腺动物体内的细菌数量显著增加。接种皮肤的浅表渗出液在无胸腺小鼠中显示出更多的中性粒细胞和吞噬的杆菌。
这些实验表明,无胸腺裸C57BL/6小鼠对实验性皮肤炭疽具有显著抗性,显然是因为一种浅表性中性粒细胞反应,该反应在接种的细菌侵入下层皮肤之前将其清除。