The Polysaccharide Capsule of Campylobacter jejuni Modulates the Host Immune Response

The Polysaccharide Capsule of Campylobacter jejuni Modulates the Host Immune Response
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DOI:
10.1128/iai.01008-12
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发表时间:
2013-03-01
影响因子:
3.1
通讯作者:
Guerry, Patricia
Guerry, Patricia
中科院分区:
医学2区
文献类型:
--
作者:
Maue, Alexander C.;Mohawk, Krystle L.;Guerry, Patricia

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空肠弯曲菌是世界范围内细菌性肠炎的主要致病菌。该生物体的特征在于多糖结构的多样性,包括多糖荚膜。大部分C。已知空肠囊用氨基磷酸酯甲酯(MeOPN)非化学计量地修饰。C. jejuni 81-176已经被证明是血清抗性所需的,但是在这里我们表明缺乏MeOPN修饰的包囊化突变体,一种mpnC突变体,与未包囊化突变体一样对血清杀伤敏感。在小鼠肠道定植模型中,与野生型81-176相比,未包封的突变体kpsM突变体表现出显著降低的定植,并且mpnC突变体表现出中等水平的定植。两种突变体都与来自固有层CD 4(+)细胞的白细胞介素17(IL-17)表达水平高于来自感染81-176的动物的细胞的白细胞介素17(IL-17)表达水平相关。此外,与野生型81-176相比,在用kpsM和mpnC突变体体外刺激人报告细胞系后,观察到Toll样受体4(TLR 4)和TLR 2活化水平降低。结果表明,C.空肠和MeOPN修饰调节宿主免疫应答。
Campylobacter jejuni is a major cause of bacterial diarrheal disease worldwide. The organism is characterized by a diversity of polysaccharide structures, including a polysaccharide capsule. Most C. jejuni capsules are known to be decorated nonstoichio-metrically with methyl phosphoramidate (MeOPN). The capsule of C. jejuni 81-176 has been shown to be required for serum resistance, but here we show that an encapsulated mutant lacking the MeOPN modification, an mpnC mutant, was equally as sensitive to serum killing as the nonencapsulated mutant. A nonencapsulated mutant, a kpsM mutant, exhibited significantly reduced colonization compared to that of wild-type 81-176 in a mouse intestinal colonization model, and the mpnC mutant showed an intermediate level of colonization. Both mutants were associated with higher levels of interleukin 17 (IL-17) expression from lamina propria CD4(+) cells than from cells from animals infected with 81-176. In addition, reduced levels of Toll-like receptor 4 (TLR4) and TLR2 activation were observed following in vitro stimulation of human reporter cell lines with the kpsM and mpnC mutants compared to those with wild-type 81-176. The data suggest that the capsule polysaccharide of C. jejuni and the MeOPN modification modulate the host immune response.