Purified lipopolysaccharide from Francisella tularensis live vaccine strain (LVS) induces protective immunity against LVS infection that requires B cells and gamma interferon
Purified lipopolysaccharide from Francisella tularensis live vaccine strain (LVS) induces protective immunity against LVS infection that requires B cells and gamma interferon
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DOI：
10.1128/iai.68.4.1988-1996.2000
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发表时间：
2000-04-01
影响因子：
3.1
通讯作者：
Elkins, KL
中科院分区：
文献类型：
--
作者：
Dreisbach, VC;Cowley, S;Elkins, KL
以往的研究结果表明，对致死性土拉氏方济氏菌活疫苗株或单核细胞增生性李斯特菌感染的非特异性保护性免疫既可以通过亚致死性感染的DTH细菌激发，也可以通过在致死攻击前3天给予细菌DNA的治疗来激发。在这里，我们表征了从图拉尔蘑菇中纯化的脂多糖(LPS)刺激类似早期保护性免疫的能力。用令人惊讶的少量LVS内毒素治疗小鼠，可以在2到3天内对致命的LVS攻击产生非常强大和持久的保护。尽管有这种强烈的保护反应，但从图拉氏方块中提纯的内毒素不能激活小鼠B细胞的增殖或多克隆免疫球蛋白的分泌，也不能激活海洋脾细胞分泌白介素4(IL-4)、白介素6(IL-6)、白介素12(IL-12)或干扰素(干扰素-γ)。纯化的LVS内毒素免疫小鼠后，可诱导较弱的特异性抗内毒素免疫球蛋白M(IgM)反应和极少量的免疫球蛋白G，而感染LVS细菌的小鼠可产生较强的抗内毒素抗体反应，尤其是IgG2a。使用各种免疫缺陷小鼠品系的研究表明，保护机制不涉及通过LPs(N)基因产物的识别；然而，保护依赖于B细胞和干扰素-γ。
Previous results have demonstrated that nonspecific protective immunity against lethal Francisella tularensis live vaccine strain (LVS) or Listeria monocytogenes infection can be stimulated either by sublethal infection dth bacteria or by treatment with bacterial DNA given 3 days before lethal challenge. Here we characterize the ability of purified lipopolysaccharide (LPS) from F. tularensis LVS to stimulate similar early protective immunity. Treatment of mice with surprisingly small amounts of LVS LPS resulted in very strong and long-lived protection against lethal LVS challenge within 2 to 3 days. Despite this strong protective response, LPS purified from F. tularensis LVS did not activate murine B cells for proliferation or polyclonal immunoglobulin secretion, nor did it activate marine splenocytes for secretion of interleukin-4 (IL-4), IL-6, IL-12, or gamma interferon (IFN-gamma). Immunization of mice with purified LVS LPS induced a weak specific anti-LPS immunoglobulin M (IgM) response and very little IgG; however, infection of mice with LVS bacteria resulted in vigorous IgM and IgG, particularly IgG2a, anti-LPS antibody responses. Studies using various immunodeficient mouse strains, including LPS-hyporesponsive C3H/HeJ mice, mu MT- (B-cell-deficient) knockout mice, and IFN-gamma-deficient mice, demonstrated that the mechanism of protection does not involve recognition through the Lps(n) gene product; nonetheless, protection was dependent on B cells as well as IFN-gamma.