Differences in gamma interferon production induced by listeriolysin O and ivanolysin O result in different levels of protective immunity in mice infected with Listeria monocytogenes and Listeria ivanovii
Differences in gamma interferon production induced by listeriolysin O and ivanolysin O result in different levels of protective immunity in mice infected with Listeria monocytogenes and Listeria ivanovii
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DOI：
10.1128/iai.71.5.2447-2454.2003
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发表时间：
2003-05-01
影响因子：
3.1
通讯作者：
Mitsuyama, M
中科院分区：
文献类型：
--
作者：
Kimoto, T;Kawamura, I;Mitsuyama, M
李斯特菌属中的两种致病性物种，单核细胞增生李斯特菌（Listeria monocytogenes）和伊氏李斯特菌（Listeria ivanovii），其特征在于分别产生属于胆固醇依赖性溶细胞素的溶血素，即伊氏溶血素O（LLO）和伊氏溶血素O（ILO）。LLO，由L.单核细胞增多症，能够诱导γ干扰素（IFN-γ）产生，并有助于产生Th 1依赖性保护性免疫。另一方面，对劳工组织的作用一无所知，由L.伊凡诺依在这方面。本研究以0.1 50%致死剂量（LD_（50））的L.单核细胞增多症和L.伊凡诺维奇。感染L.单核细胞增多症，而L. ivanovii感染没有诱导保护作用。免疫后，给予L.单核细胞增多症，而不是在那些给予L。伊凡诺维奇。为了测定溶细胞素的IFN-γ诱导活性，构建重组蛋白。重组ILO表现出比LLO显著更低的IFN-γ诱导活性。通过比较掺入LLO和ILO的嵌合体的IFN-γ诱导活性，发现LLO的结构域1至3对于IFN-γ诱导活性是关键的，而ILO中的对应物不能诱导细胞因子产生。这些结果表明，ILO诱导IFN-γ产生的能力弱是导致L. ivanovii产生有效的保护性免疫。
Two pathogenic species in the genus Listeria, Listeria monocytogenes and Listeria ivanovii, are characterized by the production of hemolysins belonging to cholesterol-dependent cytolysins, listeriollysin O (LLO) and ivanolysin O (ILO), respectively. LLO, produced by L. monocytogenes, is able to induce gamma interferon (IFN-gamma) production and contributes to the generation of Th1-dependent protective immunity. On the other hand, nothing is known about the role of ILO, produced by L. ivanovii, in this regard. In this study, we immunized mice with 0.1 50% lethal dose (LD50) of L. monocytogenes and L. ivanovii. Protective immunity against a challenge with 10 LD50 was generated in mice infected with L. monocytogenes, whereas L. ivanovii infection did not induce protection. After immunization, the level of IFN-gamma in serum samples was increased in mice given L. monocytogenes but not in those given L. ivanovii. To determine the IFN-gamma-inducing activity of cytolysins, recombinant protein was constructed. Recombinant ILO exhibited significantly lower IFN-gamma-indueing activity than LLO. By comparing the IFN-gamma-inducing activity of a chimera incorporating LLO and ILO, it was found that domains 1 to 3 of LLO were critical for IFN-gamma-inducing activity while the counterpart in ILO was unable to induce cytokine production. These results suggested that the weak ability of ILO to induce IFN-gamma production is responsible for the failure of L. ivanovii to generate effective protective immunity.