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Anti-V antigen antibody protects macrophages from Yersinia pestis-induced cell death and promotes phagocytosis

机译:抗V抗原抗体可保护巨噬细胞免受鼠疫耶尔森氏菌诱导的细胞死亡并促进吞噬作用

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The pathogenic Yersinia spp. harbor a common plasmid (pYV) essential for virulence. The plasmid encodes a type III secretion system that functions to translocate Yersinia outer proteins (Yops) into the host cytosol. Within the host cell, the Yops act to inhibit phagocytosis and induce apoptosis. One of the plasmid-encoded proteins, virulence antigen (V), is a major protective immunogen that is involved in Yop translocation. Yersinia pestis, like the enteric Yersinia spp., was both resistant to phagocytosis by and cytotoxic for J774.A1, a murine macrophage cell line. Both of these activities were dependent on culture of the bacteria at 37degreesC for 1.5-2 h before infection. However, extending the preculture period at 37degreesC to 24 h, which induced formation of a capsule, completely blocked cytotoxicity. Treating the bacteria with either rabbit polyclonal anti-V antibodies (R anti-V) or monoclonal antibody (MAb) 7.3, antibodies specific for V and protective against plague in vivo, protected J774.A1 cells from Y. pestis-induced cell death and also reversed the inhibition of phagocytosis. Whereas protection against cell cytotoxicity was afforded by the F(ab')(2) portion of R anti-V, the ability of anti-V to induce uptake of Y. pestis appeared to be dependent on the Fc portion of the Ab. The protective epitope(s) recognized by R anti-V was contained in the central region of Y. pestis V (aa 135-275) and were partially cross reactive with Y. pseudotuberculosis and Y. enterocolitica serotype 08 V antigens.
机译:致病性耶尔森氏菌。携带对毒力至关重要的通用质粒(pYV)。该质粒编码III型分泌系统,其功能是将耶尔森氏菌外蛋白(Yops)转运到宿主细胞质中。在宿主细胞内,Yops抑制吞噬作用并诱导凋亡。质粒编码的蛋白质之一,毒力抗原(V),是一种主要的保护性免疫原,与Yop易位有关。与鼠伤性耶尔森氏菌一样,鼠疫耶尔森氏菌对鼠巨噬细胞系J774.A1的吞噬作用具有抗性并具有细胞毒性。这两种活动都取决于细菌在感染前于37摄氏度培养1.5-2小时。但是,将预培养时间从37°C延长至24小时,这会诱导形成胶囊,从而完全阻断了细胞毒性。用兔多克隆抗V抗体(R anti-V)或单克隆抗体(MAb)7.3,对V特异并在体内具有抗鼠疫作用的抗体处理细菌,可保护J774.A1细胞免受鼠疫杆菌诱导的细胞死亡和还逆转了对吞噬作用的抑制作用。 R抗V的F(ab')(2)部分提供了针对细胞毒性的保护作用,而抗V诱导鼠疫耶尔森氏菌摄取的能力似乎取决于Ab的Fc部分。 R anti-V识别的保护性抗原决定簇包含在鼠疫耶尔森氏菌V(aa 135-275)的中央区域,并与假结核耶尔森氏菌和肠结肠炎耶尔森氏菌血清型08 V抗原发生部分交叉反应。

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