Deficient serum mannose-binding lectin levels and MBL2 polymorphisms increase the risk of single and recurrent Cryptosporidium infections in young children.
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.
Carmolli
Marya
M
University of Vermont College of Medicine, Unit of Infectious Diseases, Burlington, VT, USA
Duggal
Priya
P
Haque
Rashidul
R
Lindow
Janet
J
Mondal
Dinesh
D
Petri
William A
WA
Mourningstar
Phoenix
P
Larsson
Catherine J
CJ
Sreenivasan
Meera
M
Khan
Salwa
S
Kirkpatrick
B D
BD
D000818:Animals; D002648:Child; D002675:Child, Preschool; D003457:Cryptosporidiosis / Q000276:immunology*; D005260:Female; D006239:Haplotypes; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D037601:Mannose-Binding Lectin / Q000172:deficiency* / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D012307:Risk Factors; D034101:Sporozoites / Q000276:immunology
C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin