Immune modulation by a high molecular weight fraction from the rat tapeworm Hymenolepis diminuta.
The host-parasite relationship is exquisitely specific. In exploiting the host niche, a variety of helminth parasites have been shown to directly manipulate their hosts' immune responses. We assessed the ability of a whole-worm extract of Hymenolepis diminuta to modulate immune cell activation. Immune cells isolated from human blood or rodent spleens were activated with the T cell mitogen, concanavalin A (Con A) +/- H. diminuta extract and cytokine production (i.e. IL-2, -4, -10, -12) and proliferation assessed by ELISA and [3H]thymidine incorporation 24 and 72 h post-treatment, respectively. Co-treatment with the H. diminuta extract (100 microg protein/ml) virtually abolished Con A-induced immune cell proliferation, which was not due to increased apoptosis. Boiling of the worm extract reduced its anti-proliferative effect and fractionation indicated that a > 50 kDa component was predominantly responsible for the inhibition of Con A-induced immune cell proliferation. Cytokine determinations revealed that the H. diminuta extract significantly reduced Con A-stimulated IL-2 and IL-4, but enhanced the production of IFNy, IL-12 and IL-10. The increased IL-12 was due to an LPS contaminant in the extract and a helminth-derived 'IL-12'-like peptide that bound in the ELISA and Western blots. In contrast, a H. diminuta-derived factor directly stimulated IL-10 production by murine splenocytes, and contaminating LPS synergistically enhanced the production of IL-10. Thus, H. diminuta has the potential to block stimulated T cell proliferation and, by inhibiting IL-4 and promoting IL-10 production, may bias the immune environment towards one of immunoregulation and away from IL-4 dominated T helper 2 type events.
Intestinal Disease Research Programme, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5.
A
A
Wang
D M
DM
McKay
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D049109:Cell Proliferation; D015801:Helminth Proteins / Q000502:physiology*; D006801:Humans; D048190:Hymenolepis diminuta / Q000502:physiology*; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D051381:Rats; D013154:Spleen / Q000166:cytology
D015801:Helminth Proteins; D007378:Interleukins; D007371:Interferon-gamma