IMMUNE-RESPONSES TO YERSINIA-ENTEROCOLITICA IN SUSCEPTIBLE BALB/C AND RESISTANT C57BL/6 MICE - AN ESSENTIAL ROLE FOR GAMMA-INTERFERON

IMMUNE-RESPONSES TO YERSINIA-ENTEROCOLITICA IN SUSCEPTIBLE BALB/C AND RESISTANT C57BL/6 MICE - AN ESSENTIAL ROLE FOR GAMMA-INTERFERON
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DOI:
10.1128/iai.62.6.2590-2599.1994
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发表时间:
1994-06-01
影响因子:
3.1
通讯作者:
HEESEMANN, J
HEESEMANN, J
中科院分区:
医学2区
文献类型:
--
作者:
AUTENRIETH, IB;BEER, M;HEESEMANN, J

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小鼠对小肠结肠炎耶尔森氏菌感染的易感性已被证明与编码对鼠伤寒沙门氏菌和其他病原体的抗性的Ity基因座或H-2基因座均无关。我们实验室最近的研究表明,T细胞介导的免疫应答是克服原发性耶尔森氏菌感染所必需的。在本研究中,我们调查了与小肠结肠炎大肠杆菌感染的过程中,由此产生的免疫反应,在耶尔森氏菌敏感的BALB/c和耶尔森氏菌耐药的C57 BL/6小鼠。在感染的早期阶段,病原体的清除在两种小鼠品系中是相当的,表明先天抗性的机制相似。来自耶尔森氏菌感染的C57 BL/6小鼠的脾T细胞在暴露于热灭活耶尔森氏菌后表现出显著的增殖反应并产生γ干扰素(IFN-γ)。相比之下,在BALB/c小鼠中的耶尔森氏菌特异性T细胞反应较弱,并且在感染后第21天之前不能检测到IFN-γ的产生。从C57 BL/6小鼠中分离的T细胞在感染后7天介导了对小肠结肠炎耶尔森氏菌的免疫,但从BALB/c小鼠中分离的T细胞没有,而在感染后21天,两种菌株的T细胞介导了保护作用。IFN-γ的中和消除了C57 BL/6小鼠对耶尔森氏菌的抗性,但在BALB/c小鼠中的程度要小得多。重组IFN-γ或抗白细胞介素-4抗体的管理使BALB/c小鼠耐耶尔森氏菌,而这种治疗并没有显着影响C57 BL/6小鼠的感染过程。这些结果表明,细胞免疫应答,特别是由耶尔森氏菌特异性T细胞产生IFN-γ,与小鼠对耶尔森氏菌的抗性有关。小肠结肠炎
Susceptibility of mice to infection with Yersinia enterocolitica has been shown to be related to neither the Ity locus encoding for resistance to Salmonella typhimurium and other pathogens nor the H-2 locus. Recent studies in our laboratory have demonstrated that T-cell-mediated immune responses are required for overcoming primary Yersinia infection. In the present study, we investigated the course of infection with E enterocolitica and the resulting immune responses in Yersinia-susceptible BALB/c and Yersinia-resistant C57BL/6 mice. In the early phase of infection, the clearance of the pathogen,vas comparable in both strains of mice, suggesting similar mechanisms of innate resistance. Splenic T cells from Yersinia-infected C57BL/6 mice exhibited marked proliferative responses and produced gamma interferon (IFN-gamma) upon exposure to heat-killed yersiniae. By contrast, the Yersinia-specific T-cell response in BALB/c mice was weak, and IFN-gamma production could not be detected before day 21 postinfection. T cells isolated from C57BL/6 mice 7 days after infection mediated immunity to Y enterocolitica but those from BALB/c mice did not, while at 21 days postinfection T cells from both strains mediated protection. Neutralization of IFN-gamma abrogated resistance to yersiniae in C57BL/6 mice but to a far smaller extent in BALB/c mice. Administration of recombinant IFN-gamma or anti-interleukin-4 antibodies rendered BALB/c mice resistant to yersiniae, whereas this treatment did not significantly affect the course of the infection in C57BL/6 mice. These results indicate that the cellular immune response, in particular the production of IFN-gamma by Yershia-specific T cells, is associated with resistance of mice to Y. enterocolitica.