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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"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. "
[Show abstract][Hide abstract] ABSTRACT: Species of the genus Cryptosporidium are protozoan parasites (Apicomplexa) that cause gastroenteritis in animals and humans. Of these Cryptosporidium parvum and Cryptosporidium hominis are the major causative agents of human cryptosporidiosis. Whereas infection is self-limiting in the immunocompetent hosts, immunocompromised individuals develop a chronic, life-threatening disease. As specific therapeutic or preventive interventions are not yet available, better understanding of the immune response to the parasite is required. This minireview briefly summarizes the factors involved in the innate and acquired immune response in this pathogen-host interaction with an emphasis on more recent data from mouse models of infection.
Full-text · Article · Nov 2010 · Experimental Parasitology
[Show abstract][Hide abstract] ABSTRACT: Immune responses play a critical role in protection from, and resolution of, cryptosporidiosis. However, the nature of these responses, particularly in humans, is not completely understood. Both innate and adaptive immune responses are important. Innate immune responses may be mediated by Toll-like receptor pathways, antimicrobial peptides, prostaglandins, mannose-binding lectin, cytokines and chemokines. Cell-mediated responses, particularly those involving CD4(+) T cells and IFN-gamma play a dominant role. Mucosal antibody responses may also be involved. Proteins mediating attachment and invasion may serve as putative protective antigens. Further knowledge of human immune responses in cryptosporidiosis is essential in order to develop targeted prophylactic and therapeutic interventions. This review focuses on recent advances and future prospects in the understanding of human immune responses to Cryptosporidium infection.
Preview · Article · Mar 2010 · Future Microbiology
[Show abstract][Hide abstract] ABSTRACT: Cryptosporidium spp. are responsible for endemic and epidemic disease worldwide. Clinical manifestations may include acute, persistent, or chronic diarrhea, biliary, and pulmonary disease. Disease severity ranges from asymptomatic or mild to severe, intractable diarrhea with wasting depending on immune status, nutrition, and age. Transmission is fecal-oral with both human and animal reservoirs. Disease is often self limited in healthy individuals, but therapy remains a challenge in the immune-compromised. Prevention currently depends on appropriate hygiene and proper water management and treatment.
No preview · Article · Aug 2010 · European Journal of Clinical Microbiology