The neglected role of antibody in protection against bacteremia caused by nontyphoidal strains of Salmonella in African children
The neglected role of antibody in protection against bacteremia caused by nontyphoidal strains of Salmonella in African children
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DOI：
10.1172/jci33998
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发表时间：
2008-04-01
影响因子：
15.9
通讯作者：
Drayson, Mark T.
中科院分区：
文献类型：
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作者：
MacLennan, Calman A.;Gondwe, Esther N.;Drayson, Mark T.
非伤寒沙门氏菌菌株 (NTS) 是非洲儿童菌血症的常见原因。细胞介导的免疫反应控制细胞内感染，但不能防止血液中 NTS 的细胞外生长。我们研究了抗体是否可以预防马拉维儿童的 NTS 菌血症，因为我们发现这种情况主要发生在 2 岁之前，4 个月以下的婴儿相对较少发生。所有 16 个月以上健康马拉维儿童的血清均含有抗沙门氏菌抗体，并成功杀死了 NTS。杀伤作用是由补体膜攻击复合物介导的，并且在血液白细胞存在时不会增强。大多数16个月以下健康儿童的血清缺乏NTS特异性抗体，尽管补体功能正常，但缺乏抗体的血清不能杀死NTS。添加沙门氏菌特异性抗体，但不添加甘露糖结合凝集素，能够杀死 NTS。所有测试的 NTS 菌株都具有长链脂多糖和 rck 基因，这些特征可以抵抗补体介导的直接杀伤。脂多糖生物合成的破坏使得缺乏沙门氏菌特异性抗体的血清能够杀死 NTS。我们得出的结论是，马拉维儿童在 2 岁时就形成了克服 NTS 补体耐药性的沙门氏菌特异性抗体。这一发现和 NTS 菌血症的年龄发病率表明，抗体可以预防 NTS 菌血症，并支持开发诱导保护性抗体的 NTS 疫苗。
Nontyphoidal strains of Salmonella (NTS) are a common cause of bacteremia among African children. Cell-mediated immune responses control intracellular infection, but they do not protect against extracellular growth of NTS in the blood. We investigated whether antibody protects against NTS bacteremia in Malawian children, because we found this condition mainly occurs before 2 years of age, with relative sparing of infants younger than 4 months old. Sera from all healthy Malawian children tested aged more than 16 months contained anti-Salmonella antibody and successfully killed NTS. Killing was mediated by complement membrane attack complex and not augmented in the presence of blood leukocytes. Sera from most healthy children less than 16 months old lacked NTS-specific antibody, and sera lacking antibody did not kill NTS despite normal complement function. Addition of Salmonella-specific antibody, but not mannose-binding lectin, enabled NTS killing. All NTS strains tested had long-chain lipopolysaccharide and the rck gene, features that resist direct complement-mediated killing. Disruption of lipopolysaccharide biosynthesis enabled killing of NTS by serum lacking Salmonella-specific antibody. We conclude that Salmonella-specific antibody that overcomes the complement resistance of NTS develops by 2 years of life in Malawian children. This finding and the age-incidence of NTS bacteremia suggest that antibody protects against NTS bacteremia and support the development of vaccines against NTS that induce protective antibody.