Affiliation:
1. Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts
2. Diet, Genomic and Immunology Laboratory, Beltsville Human Nutrition Research Center, Beltsville, Maryland
3. Division of Gastroenterology, Tufts Medical Center, Boston, Massachusetts
Abstract
ABSTRACT
Infection with the trematode helminth
Schistosoma mansoni
results in a parasite egg-induced, CD4 T-cell-mediated, hepatointestinal granulomatous and fibrosing inflammation that varies greatly in severity, with a higher frequency of milder forms typically occurring in regions where the disease is endemic. One possible explanation for this is that in these regions the degree of inflammation is lessened by widespread concurrent infection with gastrointestinal nematodes. We tested this hypothesis by establishing a murine coinfection model in which mice were infected with the intestinal nematode parasite
Heligmosomoides polygyrus
prior to infection with
S. mansoni
. In CBA mice that naturally display a severe form of schistosomiasis, preinfection with
H. polygyrus
resulted in a marked reduction in schistosome egg-induced hepatic immunopathology, which was associated with significant decreases in the levels of interleukin-17 (IL-17), gamma interferon, tumor necrosis factor alpha, IL-23, IL-6, and IL-1β and with increases in the levels of IL-4, IL-5, IL-10, and transforming growth factor β in mesenteric lymph node cells, purified CD4 T cells, and isolated liver granuloma cells. There also were increases in liver Ym1 and forkhead box P3 transcription factor expression. In another model of high-pathology schistosomiasis induced in C57BL/6 mice by immunization with schistosome egg antigens in complete Freund's adjuvant, coinfection with the nematodes also resulted in a marked inhibition of hepatic immunopathology accompanied by similar shifts in cytokine production. These findings demonstrate that intestinal nematodes prevent Th1- and Th17-cell-mediated inflammation by promoting a strong Th2-polarized environment associated with increases in the levels of alternatively activated macrophages and T regulatory cells, which result in significant amelioration of schistosome-induced immunopathology.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
49 articles.
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