Infection with a helminth parasite prevents experimental colitis via a macrophage-mediated mechanism.
The propensity of a range of parasitic helminths to stimulate a Th2 or regulatory cell-biased response has been proposed to reduce the severity of experimental inflammatory bowel disease. We examined whether infection with Schistosoma mansoni, a trematode parasite, altered the susceptibility of mice to colitis induced by dextran sodium sulfate (DSS). Mice infected with schistosome worms were refractory to DSS-induced colitis. Egg-laying schistosome infections or injection of eggs did not render mice resistant to colitis induced by DSS. Schistosome worm infections prevent colitis by a novel mechanism dependent on macrophages, and not by simple modulation of Th2 responses, or via induction of regulatory CD4+ or CD25+ cells, IL-10, or TGF-beta. Infected mice had marked infiltration of macrophages (F4/80+CD11b+CD11c(-)) into the colon lamina propria and protection from DSS-induced colitis was shown to be macrophage dependent. Resistance from colitis was not due to alternatively activated macrophages. Transfer of colon lamina propria F4/80+ macrophages isolated from worm-infected mice induced significant protection from colitis in recipient mice treated with DSS. Therefore, we propose a new mechanism whereby a parasitic worm suppresses DSS-induced colitis via a novel colon-infiltrating macrophage population.
Smith
Philip
P
Institute of Molecular Medicine, St. James's Hospital, Trinity College Dublin, Dublin 8, Ireland.
Mangan
Niamh E
NE
Walsh
Caitriona M
CM
Fallon
Rosie E
RE
McKenzie
Andrew N J
AN
van Rooijen
Nico
N
Fallon
Padraic G
PG
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000276:immunology*; D016264:Dextran Sulfate / Q000633:toxicity; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D009092:Mucous Membrane / Q000276:immunology; D010063:Ovum / Q000276:immunology; D012550:Schistosoma mansoni; D012555:Schistosomiasis mansoni / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism
D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D016264:Dextran Sulfate