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鼠胃肠道中的铜绿假单胞菌清除是由O抗原特异性循环抗体有效介导的。

Clearance of Pseudomonas aeruginosa from the murine gastrointestinal tract is effectively mediated by O-antigen-specific circulating antibodies.

作者信息

Pier G B, Meluleni G, Goldberg J B

机构信息

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

出版信息

Infect Immun. 1995 Aug;63(8):2818-25. doi: 10.1128/iai.63.8.2818-2825.1995.

Abstract

The colonization of mucosal surfaces by Pseudomonas aeruginosa can lead to local or disseminated disease. Secretory immunoglobulin A (IgA) has been assumed to be responsible for preventing mucosal colonization by interfering with the binding of bacterial ligands to epithelial surface receptors. However, the efficacy of this mechanism of immunity derives little actual support from in vivo experiments. In an investigation of the role of local and systemic immunization strategies in reducing colonization of the gastrointestinal tract of mice by P. aeruginosa, the bacterial antigens that were potential targets for immune effectors promoting mucosal clearance were identified. Levels of gastrointestinal colonization were reduced when immunity to homologous O antigens, but not that to pili or flagella, was elicited. Oral vaccination with attenuated Salmonella typhimurium expressing P. aeruginosa serogroup O11 antigen elicited mucosal and serum IgA antibodies and serum IgG antibodies specific for the recombinant antigen. Oral challenge of immunized mice with P. aeruginosa serogroup O11 demonstrated protection against gastrointestinal colonization. Intraperitoneal immunization with a serogroup O11 high-molecular-weight O-polysaccharide antigen elicited only serum IgG and IgM antibodies yet was as effective as oral vaccination in protecting mice against gastrointestinal colonization. This finding was confirmed by the demonstration that intraperitoneal immunization with purified lipopolysaccharide was also protective against mucosal surface colonization. These results call into question the need for local immune effectors, particularly secretory IgA, directed at bacterial ligands for epithelial surface components, in protecting a mucosal surface from bacterial challenge.

摘要

铜绿假单胞菌在黏膜表面的定植可导致局部或播散性疾病。分泌型免疫球蛋白A(IgA)被认为通过干扰细菌配体与上皮表面受体的结合来防止黏膜定植。然而,这种免疫机制的有效性在体内实验中几乎没有得到实际支持。在一项关于局部和全身免疫策略在减少小鼠胃肠道中铜绿假单胞菌定植作用的研究中,确定了作为促进黏膜清除的免疫效应器潜在靶点的细菌抗原。当引发对同源O抗原而非菌毛或鞭毛的免疫时,胃肠道定植水平降低。用表达铜绿假单胞菌血清型O11抗原的减毒鼠伤寒沙门氏菌进行口服疫苗接种可引发黏膜和血清中针对重组抗原的IgA抗体以及血清IgG抗体。用铜绿假单胞菌血清型O11对免疫小鼠进行口服攻击,结果显示可预防胃肠道定植。用血清型O11高分子量O-多糖抗原进行腹腔免疫仅引发血清IgG和IgM抗体,但在保护小鼠免受胃肠道定植方面与口服疫苗接种效果相同。用纯化脂多糖进行腹腔免疫也可预防黏膜表面定植,这一结果证实了上述发现。这些结果对在保护黏膜表面免受细菌攻击时是否需要针对上皮表面成分的细菌配体的局部免疫效应器(特别是分泌型IgA)提出了质疑。

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