International Immunology Advance Access originally published online on August 14, 2009
International Immunology 2009 21(10):1125-1134; doi:10.1093/intimm/dxp078
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Protective role of mouse MBL-C on intestinal mucosa during Shigella flexneri invasion
Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, Peoples Republic of China
Correspondence to: Z.-L. Chen; E-mail: zhlchen{at}fimmu.com
Mannan-binding lectin (MBL) is a C-type serum lectin, which is believed to play an important role in the innate immunity against a variety of pathogens. MBL can bind to sugar determinants of a wide variety of microorganisms, neutralize them and inhibit infection by complement activation through the lectin pathway and opsonization by collectin receptors. Given that small intestine is a predominant site of extrahepatic expression of MBL, here we addressed the question whether MBL is involved in mucosal innate immunity. The carbohydrate recognition domain (CRD) genes of mouse MBL-C (mMBL-C) were cloned and expressed in Escherichia coli. Recombinant mMBL-C-CRD binds to Shigella flexneri 2a in a calcium-dependent manner and that interaction could be blocked by the anti-mMBL-C-CRD antibody. mMBL-C-CRD protein could inhibit the adhesion of S. flexneri 2a to intestinal mucosa, while administration of anti-mMBL-C-CRD antibody caused an increased level of bacteria adhesion in vitro. Administration of recombinant mMBL-C-CRD protein reduced the secretion of IL-6 and monocyte chemoattractant protein 1 from primary intestinal epithelial cells stimulated with S. flexneri 2a. Furthermore, neutralization of MBL activity by anti-MBL-C-CRD resulted in a significant increase in the number of S. flexneri 2a that colonized the intestines of BALB/c mice and attenuated the severity of inflammation seen in the areas of bacterial invasion. These findings suggest that mMBL-C may protect host intestinal mucosa by directly binding to the bacteria.
Keywords: bacterial invasion, carbohydrate recognition domain, mannan-binding lectin, mucosal immunity
Transmitting editor: R. A. Flavell
Received 7 January 2008, accepted 17 July 2009.