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首页> 外文期刊>Infection and immunity >Listeria monocytogenes as a Short-Lived Delivery System for the Induction of Type 1 Cell-Mediated Immunity against the p36/LACK Antigen of Leishmania major
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Listeria monocytogenes as a Short-Lived Delivery System for the Induction of Type 1 Cell-Mediated Immunity against the p36/LACK Antigen of Leishmania major

机译：单核细胞增生李斯特菌作为一种短时递送系统，可诱导针对利什曼原虫的p36 / LACK抗原的1型细胞介导的免疫。

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Listeria monocytogenes has been used as an experimental live vector for the induction of CD8-mediated immune responses in various viral and tumoral experimental models. Susceptibility of BALB/c mice to Leishmania major infection has been correlated to the preferential development of Th2 CD4 T cells through an early production of interleukin 4 (IL-4) by a restricted population of CD4 T cells which react to a single parasite antigen, LACK (stands forLeishmania homologue of receptors for activated C kinase). Experimental vaccination with LACK can redirect the differentiation of CD4+ T cells towards the Th1 pathway if LACK is coadministrated with IL-12. As IL-12 is known to be induced by L. monocytogenes, we have tested the ability of a recombinant attenuated actA mutant L. monocytogenes strain expressing LACK to induce the development of LACK-specific Th1 cells in both B10.D2 and BALB/c mice, which are resistant and susceptible toL. major, respectively. After a single injection of LACK-expressing L. monocytogenes, IL-12/p40 transcripts showed a rapid burst, and peaks of gamma interferon (IFN-γ)-secreting LACK-specific Th1 cells were detected around day 5 in the spleens and livers of mice of both strains. These primed IFN-γ-secreting LACK-reactive T cells were not detected ex vivo after day 7 of immunization but could be recruited and detected 15 days later in the draining lymph node after an L. major footpad challenge. Although immunization of BALB/c mice with LACK-expressing L. monocytogenes did not change the course of the infection withL. major, immunized B10.D2 mice exhibited significantly smaller lesions than nonimmunized controls. Thus, our results demonstrate that, in addition of its recognized use for the induction of effector CD8 T cells, L. monocytogenes can also be used as a live recombinant vector to favor the development of potentially protective IFN-γ-secreting Th1 CD4 T lymphocytes.
机译：单核细胞增生李斯特菌已被用作实验活载体，用于在各种病毒和肿瘤实验模型中诱导CD8介导的免疫反应。 BALB / c小鼠对利什曼原虫的严重感染易感性与Th2 CD4 T细胞的优先发育有关，这是由于对单个寄生虫抗原起反应的CD4 T细胞数量有限，早期产生了白介素4（IL-4）， LACK（代表活化的C激酶受体的利什曼原虫同源物）。如果将LACK与IL-12并用，则用LACK进行的实验性疫苗接种可以将CD4 + T细胞的分化重定向至Th1途径。由于已知IL-12由单核细胞增生李斯特氏菌诱导，我们已经测试了表达LACK的重组减毒actA突变单核细胞增生李斯特氏菌菌株在B10.D2和BALB / c中诱导LACK特异性Th1细胞发育的能力。具有抗药性和易感性的小鼠。专业，分别。单次注射表达LACK的单核细胞增生李斯特氏菌后，IL-12 / p40转录本迅速爆发，并在第5天左右在脾脏和肝脏中检测到分泌γ-干扰素（IFN-γ）的LACK特异性Th1细胞的峰值。两种品系的小鼠。免疫第7天后未在体内离体检测到这些引发IFN-γ分泌的LACK反应性T细胞，但15天后，在大足利什曼原虫感染后，它们可以在引流淋巴结中被募集并检测到。尽管用表达LACK的单核细胞增生李斯特氏菌对BALB / c小鼠进行免疫不会改变L的感染过程。免疫的主要B10.D2小鼠比未免疫的对照组表现出明显更小的损伤。因此，我们的结果表明，除了其公认的诱导效应CD8 T细胞的用途外，单核细胞增生李斯特氏菌还可以用作活重组载体，以促进可能分泌保护性IFN-γ的Th1 CD4 T淋巴细胞的发育。

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