Deficient Serum Mannose-Binding Lectin Levels and MBL2 Polymorphisms Increase the Risk of Single and Recurrent Cryptosporidium Infections in Young Children

University of Vermont College of Medicine, Unit of Infectious Diseases, Burlington, VT, USA
The Journal of Infectious Diseases (Impact Factor: 6). 11/2009; 200(10):1540-7. DOI: 10.1086/606013
Source: PubMed


Mannose-binding lectin (MBL) is an evolutionarily conserved protein that functions in human innate immunity by binding to microbial surfaces and promoting opsonophagocytosis. MBL has been shown to bind to Cryptosporidium sporozoites, and earlier work has suggested that the protective role of MBL may be most important in childhood. We evaluated the association between polymorphisms in the MBL gene (MBL2), serum MBL deficiency, and infection with Cryptosporidium, Entamoeba histolytica, and Giardia intestinalis in children. A large, prospective cohort of Bangladeshi preschool children was followed up for >3 years. Clinical outcomes, serum MBL levels, and MBL2 polymorphisms and haplotypes were determined. Statistically significant associations with E. histolytica and G. intestinalis were not found. Serum MBL deficiency, polymorphisms in the -221 promoter region, and the YO/XA MBL2 haplotype were strongly associated with Cryptosporidium infections, particularly recurrent infection. Children with multiple infections with Cryptosporidium were more likely to be MBL deficient (odds ratio [OR], 10.45), carry the -221 promoter variant (OR, 4.02), and have the YO/XA haplotype (OR, 4.91). We have identified a potentially important component of the human innate immune response to Cryptosporidum infection. Further work is needed to evaluate the mechanism of protection of MBL in Cryptosporidium infection.

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Available from: Rashidul Haque, Mar 19, 2014
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    • "These cells may contribute to complement synthesis at the site of C. parvum infection. A correlation of MBL deficiency and cryptosporidiosis was reported in AIDS patients with homozygous MBL gene mutations (Kelly et al., 2000) and in children with serum MBL deficiency (Carmolli et al., 2009; Kirkpatrick et al., 2006). Recently, we showed that C. parvum can activate both, the classical and lectin pathways, leading to the deposition of C3b on the parasite. "
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