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Mitogenicity of the Recombinant Mycobacterial 27-Kilodalton Lipoprotein Is Not Connected to Its Antiprotective Effect

机译:重组分枝杆菌27-Kilodalton脂蛋白的成丝性与它的抗保护作用无关。

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We reported previously that even though immunization with the recombinant mycobacterial 27-kDa lipoprotein (r27) induced a Th1-type response in mice, the vaccinated mice became more susceptible to challenge with Mycobacterium tuberculosis. In this study we show that r27 stimulates naive splenocytes to proliferate. Acylation of r27 was crucial for this effect, since a nonacylated mutant of r27, termed r27ΔSP, failed to stimulate splenocytes either in vitro or in vivo. Depletion experiments indicated that only B cells were proliferating in a T-cell-independent manner. We also found that r27 is recognized by TLR2, which is involved in mitogenic stimulation. Interestingly, r27 but not r27ΔSP induced high gamma interferon levels in splenocyte supernatants, whereas no significant interleukin-2 levels were detected. Since B-cell polyclonal activation might aggravate pathogen infection, we asked whether the antiprotective effect of the r27 lipoprotein is associated with its mitogenicity. We showed that, as in the case of r27, immunization of mice with the nonmitogenic r27ΔSP lipoprotein resulted in increased M. tuberculosis multiplication. We conclude that the antiprotective effect of the r27 lipoprotein must be linked to properties of the polypeptide portion of the lipoprotein rather than to its lipid moiety and its mitogenicity.
机译:我们以前曾报道过,即使用重组分枝杆菌27-kDa脂蛋白(r27)免疫在小鼠中引起Th1型应答,但接种疫苗的小鼠变得更容易受到结核分枝杆菌的攻击。在这项研究中,我们表明r27刺激幼稚脾细胞增殖。 r27的酰化作用对于此效应至关重要,因为称为r27ΔSP的r27的非酰化突变体无法在体外或体内刺激脾细胞。耗竭实验表明,仅B细胞以非T细胞的方式增殖。我们还发现r27被TLR2识别,这与有丝分裂刺激有关。有趣的是,r27而非r27ΔSP诱导了脾细胞上清液中的高γ干扰素水平,而未检测到明显的白介素2水平。由于B细胞多克隆激活可能会加重病原体感染,因此我们询问r27脂蛋白的抗保护作用是否与其有丝分裂性有关。我们显示,与r27一样,用非促有丝分裂性r27ΔSP脂蛋白免疫小鼠会导致 M升高。结核病繁殖。我们得出结论,r27脂蛋白的抗保护作用必须与脂蛋白的多肽部分的性质有关,而不是与其脂类部分及其有丝分裂性有关。

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