MONOCLONAL IMMUNOGLOBULIN-A PREVENTS ADHERENCE AND INVASION OF POLARIZED EPITHELIAL-CELL MONOLAYERS BY SALMONELLA-TYPHIMURIUM
MONOCLONAL IMMUNOGLOBULIN-A PREVENTS ADHERENCE AND INVASION OF POLARIZED EPITHELIAL-CELL MONOLAYERS BY SALMONELLA-TYPHIMURIUM
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DOI：
10.1016/0016-5085(94)90214-3
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发表时间：
1994-10-01
期刊：
影响因子：
29.4
通讯作者：
NEUTRA, MR
中科院分区：
文献类型：
--
作者：
MICHETTI, P;PORTA, N;NEUTRA, MR
背景/目的：肠道上皮细胞的侵袭被认为是沙门氏菌致病的关键步骤。沙门氏菌感染培养的马丁达比犬肾脏极化细胞(MDCK)是一种简单的体外模拟体内肠道细胞侵袭的系统。本研究分析分泌型免疫球蛋白(Ig)A抗体对上皮细胞侵袭的保护作用。方法：将鼠伤寒沙门氏菌作用于MDCK细胞单层，加入或不加入针对野生型鼠伤寒沙门氏菌表面抗原决定簇的聚合IgA单抗(Sal4)。结果：在Sal4IgA存在下，MDCK融合单层细胞可抵抗野生型鼠伤寒沙门氏菌的顶端侵袭，但不能抵抗缺乏Sal4表位的突变株的侵袭。保护是Sal4特异性的，依赖于顶端培养液中Sal4的浓度，并在观察到IgA-细菌复合体凝集的IgA浓度下发生。当MDCK细胞单层在与沙门氏菌孵育前进行甲醛固定以防止细菌入侵时，在没有IgA的情况下和在对照IgA存在的情况下，沙门氏菌会发生粘连，而在Sal4IgA存在的情况下不会发生粘连。结论：在缺乏其他免疫或非免疫保护机制的情况下，单用免疫球蛋白可以防止细菌黏附和侵袭上皮细胞。
Background/Aims: Invasion of the intestinal epithelium is considered a critical step in Salmonella pathogenesis. Infection by Salmonella of cultured monolayers of polarized Madin-Darby canine kidney (MDCK) cells has been established as a simple in vitro system that mimics the invasion of intestinal enterocytes in vivo. This study analyzes the protective role of secretory immunoglobulin (Ig) A antibodies against epithelial invasion. Methods: Salmonella typhimurium was applied to MDCK cell monolayers in the presence or absence of a monoclonal, polymeric IgA antibody (Sal4) directed against an antigenic determinant exposed on the surface of wild-type S. typhimurium. Results: In the presence of Sal4 IgA, confluent monolayers of MDCK cells were protected against apical invasion by wild-type S. typhimurium but not against a mutant strain that lacks the Sal4 epitope. Protection was Sal4-specific, dependent on the concentration of Sal4 in the apical medium, and occurred at IgA concentrations at which agglutination of IgA-bacterial complexes was observed. When MDCK cell monolayers were formaldehyde-fixed before incubation with Salmonella to prevent bacterial invasion, adhesion of Salmonella occurred in the absence of IgA and in the presence of control IgA but not in the presence of Sal4 IgA. Conclusions: IgA alone can prevent bacterial adherence and invasion of epithelial cells in the absence of other immune or nonimmune protective mechanisms.