McQueen C E, Boedeker E C, Le M, Hamada Y, Brown W R
Department of Gastroenterology, Walter Reed Army Institute of Research, Washington, D.C. 20307.
Infect Immun. 1992 Jan;60(1):206-12. doi: 10.1128/iai.60.1.206-212.1992.
Infection of rabbits with Escherichia coli RDEC-1 is a useful model for diarrheal disease caused by mucosally attaching E. coli. Understanding of the protective immunity induced by RDEC-1 infection in rabbits should provide information useful in the design of vaccines for protection against this infection and other mucosally attaching organisms as well. Thus, to define the time course and location of specific immunoglobulin A secretion in relation to bacterial colonization during primary RDEC-1 infection, we infected rabbits with RDEC-1, which express AF/R1 adherence pili, and compared sites of anti-AF/R1 antibody-containing cells in the intestinal mucosa with the sites of luminal colonization and mucosal attachment of RDEC-1. Also, anti-AF/R1 antibodies in intestinal fluids and bile were measured by enzyme-linked immunosorbent assay, and attachment sites of RDEC-1 to the intestinal epithelium were determined by immunohistochemical examination. Anti-AF/R1 pilus antibody-containing cells were most numerous in the proximal intestine (duodenum and jejunum). In contrast, both luminal colonization and attachment of RDEC-1 to epithelial cells were densest in the distal intestine (cecum and colon). Anti-AF/R1 antibodies were present in approximately equal amounts in fluids collected from all levels of the gut after week 1 postinfection. Anti-AF/R1 antibody levels in undiluted bile exceeded those in gut flushes by at least 2 orders of magnitude. Loss of RDEC-1 attachment to epithelial cells preceded resolution of diarrheal illness despite the presence of large numbers of organisms in the intestinal lumen. Our studies indicate that during RDEC-1 infection (i) sites of greatest mucosal anti-AF/R1 antibody secretion are proximal to sites of maximal RDEC-1 luminal colonization and attachment, (ii) bile is a major source of specific antibodies in the intestinal lumen, and (iii) interference with RDEC-1 attachment to epithelial cells may permit resolution of disease.
用大肠杆菌RDEC-1感染兔子是研究由黏膜附着性大肠杆菌引起的腹泻病的有用模型。了解RDEC-1感染兔子后诱导的保护性免疫，应为设计预防这种感染以及其他黏膜附着性微生物的疫苗提供有用信息。因此，为了确定初次RDEC-1感染期间特异性免疫球蛋白A分泌的时间进程和位置与细菌定植的关系，我们用表达AF/R1黏附菌毛的RDEC-1感染兔子，并将肠黏膜中含抗AF/R1抗体的细胞位点与RDEC-1在肠腔中的定植位点和黏膜附着位点进行比较。此外，通过酶联免疫吸附测定法测量肠液和胆汁中的抗AF/R1抗体，并通过免疫组织化学检查确定RDEC-1与肠上皮的附着位点。含抗AF/R1菌毛抗体的细胞在近端小肠（十二指肠和空肠）中最多。相比之下，RDEC-1在肠腔中的定植和与上皮细胞的附着在远端小肠（盲肠和结肠）中最为密集。感染后第1周，从肠道各水平收集的液体中抗AF/R1抗体的含量大致相等。未稀释胆汁中的抗AF/R1抗体水平比肠道冲洗液中的至少高2个数量级。尽管肠腔中有大量细菌，但RDEC-1与上皮细胞的附着丧失先于腹泻疾病的缓解。我们的研究表明，在RDEC-1感染期间：（i）黏膜抗AF/R1抗体分泌最多的位点位于RDEC-1在肠腔中最大定植和附着位点的近端；（ii）胆汁是肠腔中特异性抗体的主要来源；（iii）干扰RDEC-1与上皮细胞的附着可能使疾病得到缓解。
