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首页> 美国卫生研究院文献>Infection and Immunity >Antilisterial immunity includes specificity to listeriolysin O (LLO) and non-LLO-derived determinants.
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Antilisterial immunity includes specificity to listeriolysin O (LLO) and non-LLO-derived determinants.

机译：抗李斯特菌免疫力包括对李斯特菌溶血素O（LLO）和非LLO衍生决定簇的特异性。

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摘要

Subclinical infection of BALB/c mice with virulent Listeria monocytogenes leads to the generation of Listeria-specific T-cell populations required for the expression of protective immunity. The L. monocytogenes-produced hemolysin listeriolysin O (LLO) is a virulence factor which appears to be crucial for the induction of protective antilisterial immunity. Analysis of the specificity of antilisterial cytotoxic cells from Listeria-immune BALB/c donors has shown a dominant response to an epitope corresponding to amino acids 91 to 99 of LLO. Demonstration of antilisterial T cells with specificity to non-LLO-derived epitopes has been difficult to achieve because of the requirement of LLO in facilitating escape of the bacteria to the cytoplasm of the host cell and the apparent dominance of an anti-LLO response in antilisterial immunity. In this study we show that antilisterial immunity also includes specificity to non-LLO-derived determinants. We used as an immunogen an LLO- mutant of L. monocytogenes which expresses the hemolysin perfringolysin O (PFO). The LLO- PFO+ L. monocytogenes mutant possesses invasive properties similar to those of wild-type L. monocytogenes and escape from the phagocytic vacuole because of the activity of PFO. We found that J774 target cells infected with the LLO- PFO+ L. monocytogenes mutant were lysed by antilisterial cytotoxic T cells obtained from BALB/c mice immunized with wild-type L. monocytogenes. In addition, BALB/c mice immunized with the LLO- PFO+ L. monocytogenes mutant were immune to challenge with LLO+ wild-type L. monocytogenes, a finding indicative of protective antilisterial immunity specific to Listeria-derived epitopes other than LLO. Spleen cells from BALB/c mice immunized with the LLO- PFO+ L. monocytogenes mutant adoptively transferred antilisterial protection to a subsequent challenge with wild-type L. monocytogenes. This splenocyte population also contained cytotoxic cells which lysed target cells infected with either the LLO- PFO+ L. monocytogenes mutant or wild-type LLO+ L. monocytogenes but did not lyse target cells infected with an LLO-expressing Bacillus subtilis transformant. These results establish that during the immune response to L. monocytogenes, immune splenocytes with specificity for LLO and other, non-LLO-derived epitopes develop. These non-LLO epitopes serve as targets for antilisterial cytotoxic cells and for lymphocytes which adoptively transfer antilisterial immunity.
机译：具有毒性的单核细胞增生李斯特菌的BALB / c小鼠的亚临床感染导致表达保护性免疫所需的李斯特菌特异性T细胞群的产生。单核细胞增生李斯特氏菌产生的溶血素李斯特菌溶血素O（LLO）是一种毒力因子，似乎对诱导保护性抗李斯特菌免疫至关重要。对来自利斯特氏菌免疫的BALB / c供体的抗李斯特菌细胞毒性细胞的特异性分析表明，它对对应于LLO氨基酸91至99的表位具有显性反应。由于LLO有助于细菌向宿主细胞胞质的逃逸以及抗LLO应答在抗李斯特菌中的明显优势，因此难以实现对非LLO衍生表位具有特异性的抗李斯特菌T细胞的展示免疫。在这项研究中，我们表明抗李斯特菌免疫还包括对非LLO衍生决定簇的特异性。我们将表达溶血素溶血性溶血素溶血素O（PFO）的单核细胞增生李斯特氏菌的LLO突变体用作免疫原。 LLO-PFO +单核细胞增生李斯特氏菌突变体具有与野生型单核细胞增生李斯特氏菌相似的侵袭特性，并且由于PFO的活性而逃离吞噬液泡。我们发现感染了LLO-PFO +单核细胞增生李斯特氏菌突变体的J774目标细胞被抗李斯特菌细胞毒性T细胞裂解，该细胞从用野生型单核细胞增生李斯特菌免疫的BALB / c小鼠获得。另外，用LLO-PFO +单核细胞增生李斯特氏菌突变体免疫的BALB / c小鼠对LLO +野生型单核细胞增生李斯特氏菌免疫免疫，这一发现表明除LLO以外，对李斯特菌来源的表位具有特异性的保护性抗李斯特菌免疫力。用LLO-PFO +单核细胞增生李斯特氏菌突变体免疫的BALB / c小鼠的脾细胞过继转移抗李斯特菌的保护作用至随后的野生型单核细胞增生李斯特氏菌攻击。该脾细胞群体还含有细胞毒性细胞，其溶解被LLO-PFO +单核细胞增生李斯特氏菌突变体或野生型LLO +单核细胞增生李斯特氏菌感染的靶细胞，但不裂解被表达LLO的枯草芽孢杆菌转化子感染的靶细胞。这些结果表明，在对单核细胞增生李斯特氏菌的免疫应答过程中，会产生对LLO和其他非LLO衍生表位具有特异性的免疫脾细胞。这些非LLO表位用作抗李斯特菌细胞毒性细胞和过继转移抗李斯特菌免疫力的淋巴细胞的靶标。

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