Mannose-binding lectin is a component of innate mucosal defense against Cryptosporidium parvum in AIDS

Background & Aims: Nonimmune mechanisms of mucosal defense seem to be biolo gically important and might explain the observed variability in the course of enteric infection in immunodeficiency, Mannose-binding lectin (MBL) defi ciency is associated with persistent diarrhea in children, We found that ge netic determinants of MBL deficiency appear to predispose to cryptosporidio sis in patients with the acquired immunodeficiency syndrome (AIDS), and wen t on to study interactions of MBL and complement on Cryptosporidium parvum sporozoites. Methods: This study involved cross-sectional study of MBL geno type and enteric infection in 72 Zambian AIDS patients with diarrhea, immun ofluorescence analysis of MBL and C4 binding to C. parvum, and immunoblotti ng for MBL and complement in small intestinal fluid, Results: individuals h omozygous for MBL structural gene mutations were at increased risk of crypt osporidiosis (odds ratio, 8.2; 95% confidence interval, 1.5-42; P = 0.02). Lectin-mediated and concentration-dependent binding of purified MBL was det ected on sporozoites but not oocysts, and MBL activated C4 on sporozoites, MEL, C3, C4, and albumin were detected in small intestinal fluid in half th e patients tested, suggesting transexudation of serum components into the e nteropathic gut, Conclusions: The increased risk of cryptosporidiosis in ME L deficiency appears to include patients with AIDS. It may operate through MEL-mediated complement activation on sporozoites.