Infection with a Helminth Parasite Prevents Experimental Colitis via a Macrophage-Mediated Mechanism

Abstract

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-β. 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.

A Helminth Immunomodulator Reduces Allergic and Inflammatory Responses by Induction of IL-10-Producing Macrophages

“…Thus, cystatin-treated macrophages resembled type II-activated macrophages (42). Just recently it has been shown that infection with the trematode parasite S. mansoni prevents experimental colitis via a macrophage-mediated mechanism (43). We are currently studying the molecular mechanisms of immune modulation by filarial cystatin, such as the signaling pathways involved and the domains of cystatin responsible for the described effects.…”

Exacerbation of Oxazolone Colitis by Infection with the Helminth Hymenolepis diminuta

“…1 Collectively, these studies have shown that as a consequence of the host response to infection with helminth parasites, there is mobilization of transforming growth factor (TGF)-␤, interleukin (IL)-10, Foxp3 ϩ regulatory T cells, alternatively activated macrophages, and inhibition of IL-17-and interferon (IFN)-␥-driven events: one, or a combination, of these events could block the development of autoimmune and inflammatory disorders. [2][3][4][5][6][7] These findings have been complemented by intriguing data suggesting that infection with viable parasitic nematodes could be a treatment for patients with inflammatory bowel disease (IBD) 8 or asthma, 9 whose condition is not managed by conventional therapies.…”

Interleukin 37 expression protects mice from colitis

“…and P.J.) blinded to the time point, strain, and treatment groups, as per published methods (28,29).…”