Complement is activated during Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS). There is evidence of complement activation via the alternative pathway in STEC-HUS patients as well as from in vivo and in vitro models. Ozaki et al. demonstrate activation of the mannose-binding lectin (MBL) pathway in Shiga toxin-treated mice expressing human MBL2, but lacking murine Mbls. Treatment with anti-human MBL2 antibody was protective, suggesting that MBL pathway activation also contributes to Shiga toxin-mediated renal injury.