Differential Killing of Salmonella enterica Serovar Typhi by Antibodies Targeting Vi and Lipopolysaccharide O:9 Antigen.
Differential Killing of Salmonella enterica Serovar Typhi by Antibodies Targeting Vi and Lipopolysaccharide O:9 Antigen.
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DOI：
10.1371/journal.pone.0145945
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
MacLennan CA
中科院分区：
文献类型：
--
作者：
Hart PJ;O'Shaughnessy CM;Siggins MK;Bobat S;Kingsley RA;Goulding DA;Crump JA;Reyburn H;Micoli F;Dougan G;Cunningham AF;MacLennan CA
伤寒沙门氏菌（Salmonella enterica serovar Typhi）表达Vi多糖的荚膜，而大多数沙门氏菌血清型，包括S.肠炎沙门氏菌和S.鼠伤寒，不要。两个S。伤寒和沙门氏菌。肠杆菌表达脂多糖O：9抗原，但几乎没有证据表明抗O：9抗体的交叉保护作用。基于Vi多糖的疫苗具有针对伤寒的效力，表明针对Vi的抗体赋予保护作用。在这里，我们调查的作用，Vi胶囊和抗体对Vi和O：9抗体依赖的补体和吞噬细胞介导的沙门氏菌的杀伤。使用表达Vi和不表达Vi的S.伤寒和沙门氏菌。鼠伤寒沙门氏菌S.伤寒对血清和血液比沙门氏菌更敏感。鼠伤寒。Vi表达赋予人血液中对补体介导的和吞噬细胞介导的抗体依赖性杀伤模式的增加的抗性。Vi胶囊与C3和C5 b-9沉积减少以及与S的总体抗体结合减少相关。伤寒然而，纯化的人抗Vi抗体在补体存在下能够杀死表达Vi的沙门氏菌，而抗O：9抗体的杀死与Vi表达负相关。耗尽针对除Vi以外的抗原的抗体的人血清保留杀死表达Vi的细菌的能力。我们的研究结果支持Vi胶囊在防止沙门氏菌的补体和吞噬细胞杀伤中的保护作用，其可以被特异性抗Vi抗体克服，但仅在有限程度上被抗O：9抗体克服。
Salmonella enterica serovar Typhi expresses a capsule of Vi polysaccharide, while most Salmonella serovars, including S. Enteritidis and S. Typhimurium, do not. Both S. Typhi and S. Enteritidis express the lipopolysaccharide O:9 antigen, yet there is little evidence of cross-protection from anti-O:9 antibodies. Vaccines based on Vi polysaccharide have efficacy against typhoid fever, indicating that antibodies against Vi confer protection. Here we investigate the role of Vi capsule and antibodies against Vi and O:9 in antibody-dependent complement- and phagocyte-mediated killing of Salmonella. Using isogenic Vi-expressing and non-Vi-expressing derivatives of S. Typhi and S. Typhimurium, we show that S. Typhi is inherently more sensitive to serum and blood than S. Typhimurium. Vi expression confers increased resistance to both complement- and phagocyte-mediated modalities of antibody-dependent killing in human blood. The Vi capsule is associated with reduced C3 and C5b-9 deposition, and decreased overall antibody binding to S. Typhi. However, purified human anti-Vi antibodies in the presence of complement are able to kill Vi-expressing Salmonella, while killing by anti-O:9 antibodies is inversely related to Vi expression. Human serum depleted of antibodies to antigens other than Vi retains the ability to kill Vi-expressing bacteria. Our findings support a protective role for Vi capsule in preventing complement and phagocyte killing of Salmonella that can be overcome by specific anti-Vi antibodies, but only to a limited extent by anti-O:9 antibodies.