The role of TGF-β in mice infected with Heligmosomoides polygyrus

Authors


: Maria Doligalska, Department of Parasitology, Institute of Zoology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland (e-mail: mdolig@biol.uw.edu.pl).

SUMMARY

Hyporesponsiveness induced by Heligmosomoides polygyrus was quantified and the relationship between TGF-β and inflammation was identified in BALB/c mice. The immune response and pathological changes modified by neutralization of TGF-β were characterized in vivo. Nine and twelve days following infection, BALB/c mice were injected intraperitoneally with anti-TGF-β (1,2,3) antibodies, isotype control antibodies or isosmotic solution. We assessed both Th1 and Th2 related cytokines production ex vivo and in vitro, IgA, the number of CD4+ cells, and eosinophils in the lamina propria and the villus : crypt ratio in the small intestine 6 weeks after infection. The pattern of cytokine production differed in the intestine, peritoneal fluid and serum. In mice infected with H. polygyrus the concentrations of IL-5, IL-12, TNF-α and IL-10 were raised in the intestine, but in serum the level of cytokines was diminished below the value observed in uninfected mice. The neutralization of TGF-β converted the pattern of immune response induced by H. polygyrus. The elevation of cytokines in serum coincided with the reduction of cytokine concentration in the intestine or peritoneum. Neutralization of TGF-β restored infiltration of eosinophils into the lamina propria of the intestine despite the low level of IL-5. We conclude that H. polygyrus infection suppresses the immune response through pathways involving TGF-β production or activity and that the Th2 related immune response was not affected by neutralization.

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