Parasitology



Immune modulation by a high molecular weight fraction from the rat tapeworm Hymenolepis diminuta


A. WANG a1 and D. M. McKAY a1c1
a1 Intestinal Disease Research Programme, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5

Article author query
wang a   [PubMed][Google Scholar] 
mckay dm   [PubMed][Google Scholar] 

Abstract

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 μg 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 IFNγ, 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.

(Received August 6 2004)
(Revised November 4 2004)
(Accepted November 5 2004)


Key Words: cestode; cytokines; host-parasite interaction.

Correspondence:
c1 Tel: +905 525 9140 ext. 22588. Fax: +905 522 3454. E-mail: mckayd@mcmaster.ca


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