Analysis of mannose-binding lectin genotypes and the association with Candida albicans and Mycobacterium tuberculosis infection ex vivo

• Main Authors: Yu-Ting Chung, 鐘于婷
• Other Authors: Tsun-Mei Lin
• Format: Others
• Language: en_US
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/37231835203484296344

碩士 === 國立成功大學 === 醫學檢驗生物技術學系 === 95 === Mannose-binding lectin (MBL) is a serum collectin that mediates activation of complement system and is important in innate immunity. Deficiency of MBL is associated with a risk of various infections and arises from structure gene mutation in exon 1 and/or the presence of a low efficiency promoter. In this study, we analyzed the frequencies of haplotypes and genotypes of MBL-2 gene polymorphisms in 588 unrelated Chinese adults and 170 tuberculosis (TB) patients. In Chinese general population, the frequency of the codon 54 mutation of the MBL-2 gene was 17.9 % (210/1176). Additionally, for two polymorphisms at position -550 and -221 in the promoter region, the frequency of several genotypes were: HY/HY, 19.2 %; HY/LY, 28.9 %; LY/LY, 16.0 %; HY/LX, 15.1 %； LX/LY, 16.0 %; LX/LX 4.8 %. Compared with TB patients, we found that main contribution to the significant p value is due to extreme high frequency of genotypes (H/H) that corresponding to high serum MBL in patients with TB versus age-matched control subjects (28.2 % vs. 17.3 %, respectively; p = 0.018). In this study, we try to clarify the role of MBL on TB infection by ex vivo assay. We found that the phagocytosis percentage and mean fluorescence intensity (MFI) of FITC labelled M. tuberculosis in peripheral blood monocytes were not difference between high-MBL phenotypes and low-MBL individuals. However, opsonophagocytosis of M. tuberculosis by monocytes may be influenced by heat labile factors. Some previous in vivo and in vitro studies have demonstrated MBL participated in the first-line defense against Candida albicans (C. albicans), an opportunistic fungal pathogen. However, the influence of individual with various MBL-2 genotypes on yeast phagocytosis and growth are still unknown. We also established an ex vivo system to illustrate the impact of MBL on C. albicans infection. Our data demonstrated that the opsonophagocytosis of monocytes and neutrophils (24.2 % vs. 11.3 %; p = 0.0004, 9.2 % vs. 3.1 %; p = 0.0157, respectively), and C. albicans growth inhibition by plasma from high MBL phenotypes were significantly higher than low MBL phenotypes (42 % vs. 18 %; p = 0.0391). These findings indicate the genotypes of MBL-2 may predict the host infection susceptibility during compromised immune defenses. It is usefully for the predictive and prevention medicine in the future.