Protective role of mouse MBL-C on intestinal mucosa during Shigella flexneri invasion.
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.
Zuo
Da-Ming
DM
Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
Zhang
Li-Yun
LY
Lu
Xiao
X
Liu
Ying
Y
Chen
Zheng-Liang
ZL
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000276:immunology / Q000378:metabolism; D004405:Dysentery, Bacillary / Q000276:immunology*; D007113:Immunity, Innate; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D007421:Intestine, Small / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D037601:Mannose-Binding Lectin / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D012763:Shigella flexneri / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D018932:Chemokine CCL2; D015850:Interleukin-6; D037601:Mannose-Binding Lectin; D014409:Tumor Necrosis Factor-alpha
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