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首页> 外文期刊>Infection and immunity >Priming of Protective Anti-Listeria monocytogenes Memory CD8+ T Cells Requires a Functional SecA2 Secretion System
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Priming of Protective Anti-Listeria monocytogenes Memory CD8+ T Cells Requires a Functional SecA2 Secretion System

机译：保护性抗李斯特菌单核细胞增生性记忆CD8 + T细胞的启动需要功能性SecA2分泌系统

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The SecA2 auxiliary secretion system of Gram-positive bacteria promotes the export of virulence proteins essential for colonization of the host in the case of both Mycobacterium tuberculosis and Listeria monocytogenes, two intracellular bacteria causing diseases in humans. We and others have demonstrated that this secretion system is also linked to the onset of long-term CD8+ T cell-mediated protective immunity in mice. In the case of L. monocytogenes, expression of SecA2 inside the cytosol of infected cells correlates with the generation of CCL3-secreting memory CD8+ T cells that are required for protection against secondary challenge with wild-type (wt) L. monocytogenes. Since the SecA2 ATPase is well conserved among Gram-positive pathogenic bacteria, we hypothesized that SecA2 itself bears evolutionarily conserved motifs recognized by cytosolic pattern recognition receptors, leading to signaling events promoting the differentiation of CCL3+ memory CD8+ T cells. To test this possibility, we generated a stable L. monocytogenes chromosomal mutant that expressed a SecA2 ATPase bearing a mutated nucleotide binding site (NBS). Similarly to a SecA2 deletion mutant, the NBS mutant exhibited rough colonies, a bacterial chaining phenotype, an impaired protein secretion profile, and in vivo virulence in comparison to wt L. monocytogenes. Importantly, mice immunized with the SecA2 NBS mutant were not protected against secondary infection with wt L. monocytogenes and did not develop CCL3+ memory CD8+ T cells. NBS mutant and wt SecA2 proteins were expressed to comparable extents by bacteria, suggesting that SecA2 itself is unlikely to promote the induction of these cells. Rather, one or several of the SecA2 substrate proteins released inside the cytosol of infected cells may be involved.
机译：革兰氏阳性细菌的SecA2辅助分泌系统促进结核分枝杆菌和单核细胞增生李斯特菌（两种引起人类疾病的细胞内细菌）对宿主定殖必不可少的毒力蛋白的输出。我们和其他人已经证明，这种分泌系统也与小鼠长期CD8 + T细胞介导的保护性免疫的发作有关。就单核细胞增生李斯特菌而言，感染细胞胞质内SecA2的表达与分泌CCL3的记忆CD8 + T细胞的生成有关，而这些细胞是保护野生型继发性攻击所必需的（ wt）单核细胞增生李斯特氏菌。由于SecA2 ATPase在革兰氏阳性致病菌中保存良好，因此我们假设SecA2本身具有被胞质模式识别受体识别的进化保守基序，从而导致促进CCL3 + 记忆CD8分化的信号事件。 sup> + T细胞。为了测试这种可能性，我们生成了稳定的单核细胞增生李斯特氏菌染色体突变体，该突变体表达了带有突变核苷酸结合位点（NBS）的SecA2 ATPase。与SecA2缺失突变体相似，与单核细胞增生李斯特菌相比，NBS突变体显示出粗糙的菌落，细菌链表型，受损的蛋白质分泌特征和体内毒力。重要的是，用SecA2 NBS突变体免疫的小鼠不能抵抗单核细胞增生李斯特氏菌的继发感染，也不能发育CCL3 + 记忆CD8 + T细胞。 NBS突变体和wt SecA2蛋白在细菌中表达的程度相当，这表明SecA2本身不太可能促进这些细胞的诱导。而是，可能涉及在感染细胞的细胞质内释放的一种或几种SecA2底物蛋白。

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