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首页> 外文期刊>Infection and immunity >Levels of Expression and Immunogenicity of Attenuated Salmonella enterica Serovar Typhimurium Strains Expressing Escherichia coli Mutant Heat-Labile Enterotoxin
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Levels of Expression and Immunogenicity of Attenuated Salmonella enterica Serovar Typhimurium Strains Expressing Escherichia coli Mutant Heat-Labile Enterotoxin

机译：表达大肠杆菌突变热不稳定肠毒素的减毒小肠沙门氏菌鼠伤寒沙门氏菌的表达水平和免疫原性

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摘要

The effects of heterologous gene dosage as well as Salmonella typhimurium strain variability on immune response toward both the heterologous antigen, the nontoxic mutant of the Escherichia coli heat-labile enterotoxin LTK63, and the carrierSalmonella strain have been analyzed. Effects of a single integration into the host DNA and different-copy-number episomal vectors were compared in S. typhimurium Δcya Δcrp Δasd strains of two different serotypes, UK-1 and SR-11. Expression of the enterotoxin in the different Salmonellaisolates in vitro was found to vary considerably and, for the episomal vectors, to correlate with the plasmid copy number. LTK63-specific serum immunoglobulin G (IgG) and mucosal immunoglobulin A (IgA) antibodies were highest in mice immunized with the high-level-expression strain. High anti-LTK63 IgG and IgA titers were found to correspond to higher anti-Salmonella immunity, suggesting that LTK63 exerts an adjuvant effect on response to the carrier. Statistically significant differences in anti-LTK63 immune response were observed between groups of mice immunized with the attenuated Δcya Δcrp UK-1 and SR-11 derivatives producing the antigen at the same rate. These data indicate that the same attenuation in S. typhimurium strains of different genetic backgrounds can influence significantly the immune response toward the heterologous antigen. Moreover, delivery of the LTK63 enterotoxin to the immune system by attenuated S. typhimurium strains is effective only when synthesis of the antigen is very high during the initial phase of invasion, while persistence of the S. typhimurium strain in deep tissues has only marginal influence.
机译：异源基因剂量以及鼠伤寒沙门氏菌菌株变异性对异源抗原，大肠杆菌热不稳定肠毒素LTK63的无毒突变体和异源抗原的免疫反应的影响分析了沙门氏菌的携带株。在 S中比较了单次整合入宿主DNA和不同拷贝数游离型载体的作用。两种不同血清型UK-1和SR-11的鼠伤寒ΔcyaΔcrpΔasd菌株。发现肠毒素在不同沙门氏菌体外分离物中的表达差异很大，而对于游离型载体，其与质粒拷贝数相关。在用高表达菌株免疫的小鼠中，LTK63特异性血清免疫球蛋白G（IgG）和粘膜免疫球蛋白A（IgA）抗体最高。发现较高的抗LTK63 IgG和IgA滴度对应较高的抗沙门氏菌免疫力，这表明LTK63对载体的应答具有佐剂作用。用减毒的Δ cyaΔcrp UK-1和SR-11衍生物以相同的速率免疫的小鼠组之间，观察到抗LTK63免疫反应的统计学差异。这些数据表明 S中的衰减相同。遗传背景不同的鼠伤寒沙门氏菌菌株可以显着影响针对异源抗原的免疫反应。此外，LTK63肠毒素通过减弱的 S传递至免疫系统。鼠伤寒菌株仅在侵袭初期抗原合成非常高而 S持续存在时才有效。深度组织中的鼠伤寒菌株仅具有很小的影响。

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