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Title: Co-Infection With Intestinal Helminths Markedly Reduces Proinflammatory Cytokines And Disease Severity In Natural And Induced High-Pathology Schistosomiasis

Author
item BAZZONE, LINDSEY - Tufts University
item SMITH, PATRICK - Tufts University
item RUTITZKY, LAURA - Tufts University
item SHAINHEIT, MARA - Tufts University
item Urban, Joseph
item SETIAWAN, TOMMY - Tufts University
item BLUM, ARTHUR - Tufts University
item WEINSTOCK, JOEL - Tufts University
item STADECKER, MIGUEL - Tufts University

Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/18/2008
Publication Date: 11/1/2008
Citation: Bazzone, L., Smith, P., Rutitzky, L., Shainheit, M., Urban Jr, J.F., Setiawan, T., Blum, A., Weinstock, J., Stadecker, M. 2008. Co-Infection with intestinal helminths markedly reduces proinflammatory cytokines and disease severity in natural and induced high-pathology Schistosomiasis. Infection and Immunity. 76(11):5164-72.

Interpretive Summary: Free ranging livestock and humans in areas of the world where parasitic infection is endemic face routine exposure to multiple pathogens. Worm infections are among those that are most common because of the fecal to oral route of exposure that is typical with poor hygiene or high densities of animals in limited areas. Studies of natural populations of infected animals and humans show a generalized depression of the immune system that often compounds the effective clearance of parasitic worms; however there are also consequences to the immune-based pathology and tissue destruction that are often a component of these infections. The current study examined the interaction between a nematode parasite that resides solely in the small intestine and a trematode parasite that resides in the mesenteric veins, but produces eggs that lodge in the liver and intestine and produce severe tissue proliferation that reduces organ function. It was observed that the nematode, because of the property to reduce a class of protein messenger molecules including interferon gamma, interleukin-17, and tumor necrosis factor alpha, reduced the intensity of the tissue response to the eggs. These results indicate that parasitic nematodes can be important as regulators of disease and sources of molecules that can activate these conditions without having to infect animals or humans. This information is important to members of the scientific community interested in reducing disease from parasitic infection, and animal scientists that study the control of infections that limit the productivity of economically important livestock species.

Technical Abstract: Infection with the trematode helminth Schistosoma mansoni results in a parasite egg-induced, CD4 T cell-mediated, hepato-intestinal granulomatous and fibrosing inflammation that varies greatly in severity, with a higher frequency of milder forms typical in endemic areas. One possible explanation is that in these areas the degree of inflammation is lessened by widespread concurrent infection with gastro-intestinal nematodes. We tested this hypothesis by establishing a murine co-infection model in which mice were given the intestinal nematode parasite Heligmosomoides polygyrus prior to infection with S. mansoni. In CBA mice that naturally display a severe form of schistosomiasis, pre-infection with H. polygyrus caused a marked reduction in granulomatous pathology associated with a significant decrease in IFN-alpha, IL-17 and TNF-alpha, as well as IL-23, IL-6 and IL-1, together with an increase in IL-4, IL-5 and IL-10, in mesenteric lymph node cells, purified CD4 T cells, or isolated liver granuloma cells. The presence of H. polygyrus did not affect the schistosome population, but the double-infected mice failed to efficiently expel the intestinal nematodes. In another model of high pathology schistosomiasis induced in BL/6 mice by immunization with schistosome egg Ag in CFA, the nematode co-infection also caused a marked inhibition of immunopathology accompanied by similar shifts in cytokine production. These findings support the notion that intestinal nematodes down-modulate Th1 and Th17 cell-mediated inflammation by promoting a strong Th2 response, which results in significant amelioration of schistosome-induced immunopathology.