Antibody-independent, interleukin-17A-mediated, cross-serotype immunity to pneumococci in mice immunized intranasally with the cell wall polysaccharide
Antibody-independent, interleukin-17A-mediated, cross-serotype immunity to pneumococci in mice immunized intranasally with the cell wall polysaccharide
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DOI：
10.1128/iai.74.4.2187-2195.2006
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发表时间：
2006-04-01
影响因子：
3.1
通讯作者：
Anderson, PW
中科院分区：
文献类型：
--
作者：
Malley, R;Srivastava, A;Anderson, PW
对肺炎链球菌的血清型特异性免疫是由对荚膜多糖的抗体赋予的，其定义了90种已知的血清型。抗同种细胞壁多糖（C-Ps）抗体是否具有保护作用一直是一个有争议的问题。在这里，我们表明，鼻内给予C-Ps与粘膜佐剂增加小鼠对实验性鼻咽部定植的胶囊化S。血清型6 B肺炎。这种免疫可以在先天缺乏免疫球蛋白的小鼠中诱导，但依赖于CD 4（+）T细胞。通过C-Ps的N乙酰化消除聚合物主链上的带电氨基降低了免疫力，在攻击时用细胞因子白细胞介素-17A的抗体治疗小鼠也是如此，两者都与由于聚合物的两性离子基序而导致T细胞活化的假设一致。C-Ps在致死性吸入性肺炎模型中也受到严重包囊化血清型3的保护。这些发现提示了一种新的抗沙门氏菌的免疫策略。肺炎。
Serotype-specific immunity to Streptococcus pneumoniae is conferred by antibodies to the capsular polysaccharides, which define the 90 known serotypes. Whether antibody to the species-common cell wall polysaccharide (C-Ps) is protective has been a matter of controversy. Here we show that C-Ps given intranasally with mucosal adjuvant increased the resistance of mice to experimental nasopharyngeal colonization by capsulated S. pneumoniae of serotype 6B. This immunity could be induced in mice congenitally lacking immunoglobulin but was dependent upon CD4(+) T cells. Elimination of the charged amino group on the polymer backbone by N acetylation of C-Ps reduced the immunity, as did treatment of the mice with antibody to the cytokine interleukin-17A at the time of challenge, both consistent with the hypothesis of T-cell activation due to the zwitterionic motif of the polymer. C-Ps also protected in a model of fatal aspiration pneumonia by heavily capsulated serotype 3. These findings suggest a novel immunization strategy against S. pneumoniae.