Toll-free autoimmunity

Proteins secreted by parasite eggs might hold the key to the next antiinflammatory therapy. On page 1319, Smith and colleagues describe the first chemokine binding protein (CKBP) produced by a human pathogen and show that it can suppress acute inflammation in disease models. The blood-dwelling worm Schistosoma mansoni takes advantage of the host’s immune system in two ways. It subverts specific inflammatory cells to help move its eggs from the intestinal vasculature to the feces, where they can be shed. It also suppresses the immune response in order to establish chronic infections, in part as shown here by keeping other inflammatory cells away from the eggs. This selective cell recruitment was not due solely to cytokine modulation, a known schistosome ability. As viruses produce chemokine binding proteins to neutralize host chemokines, the authors investigated whether S. mansoni might also make a chemokine binding protein to mask the eggs from strong inflammation. Smith and colleagues now identify a novel CKBP (smCKBP) that is secreted from schistosome eggs. This protein bound to the chemokines CXCL8 and CCL3 and prevented them from binding to their receptors on immune cells. Injecting mice with recombinant smCKBP blocked chemokinemediated neutrophil infiltration in response to a variety of inflammatory stimuli. This treatment, however, had no effect on chronic inflammation disorders such as arthritis. The authors suggest that, in nature, the parasite eggs secrete smCKBP to keep neutrophils and macrophages out of the surrounding granuloma so as not to attract immune attention, but pinning this mechanism down will require further study. Already tolerated by infected humans, smCKBP holds great potential as a new therapy for acute inflammatory diseases, especially those caused by neutrophilia.