Characterization of the immuno-regulatory response to the tapeworm Hymenolepis diminuta in the non-permissive mouse host.
Hymenolepis diminuta is spontaneously expelled from mice; concomitant with worm expulsion was protection against colitis induced by dinitrobenzene sulphonic acid (DNBS). Here we examined the immune response mobilized by Balb/c and C57Bl/6 male mice in response to H. diminuta and assessed the requirement for CD4+ cells (predominantly T cells) in worm expulsion and the anti-colitic effect. Wild-type (CD4+) or CD4 knock-out (CD4-/-) mice received five H. diminuta cysticercoids and segments of jejunum and mesenteric lymph nodes (MLNs), or spleen, were excised 5, 8 and 1l days later for mRNA analysis and cytokine production, respectively. In separate experiments uninfected and infected mice received DNBS by intra-rectal infusion and indices of inflammation were assessed 3 days later (i.e. 11 days p.i.). Infection of Balb/c mice resulted in a time-dependent increase in intestinal mRNA for Foxp3, a marker of natural regulatory T cells, and markers of alternatively activated macrophages (arginase-1, FIZZ1), while concanavalin-A activation of MLN cells revealed a significant increase in T helper 2 (TH2) type cytokines: IL-4, -5, -9, -10, -13. MLN cells showed a reduced ability to induce Foxp3 expression upon stimulation. CD4-/- mice did not display this response to infection, but surprisingly did expel H. diminuta. Moreover, DNBS-induced colitis in CD4-/- mice (wasting, tissue damage, elevated myeloperoxidase) was not reduced by H. diminuta infection, whereas time-matched infected CD4+ C57Bl/6 mice had significantly less DNBS-induced inflammation.


CONCLUSIONS
(i) in addition to stereotypical TH2 events, H. diminuta-infected Balb/c mice develop a local immuno-regulatory response; and (ii) CD4+ cells are not essential for H. diminuta expulsion from mice but are critical in mediating the anti-colitic effect that accompanies infection in this model.
Persaud
Robin
R
Intestinal Disease Research Programme, McMaster University, Hamilton, Ont., Canada.
Wang
Arthur
A
Reardon
Colin
C
McKay
Derek M
DM
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004139:Dinitrofluorobenzene / Q000031:analogs & derivatives; D004198:Disease Susceptibility; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000276:immunology; D006790:Host-Parasite Interactions / Q000276:immunology; D006925:Hymenolepiasis / Q000276:immunology*; D048190:Hymenolepis diminuta / Q000276:immunology* / Q000502:physiology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology / Q000469:parasitology; D017136:Ion Transport; D007583:Jejunum / Q000276:immunology / Q000469:parasitology; D008262:Macrophage Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D012333:RNA, Messenger; D016753:Interleukin-10; C045305:2,4-dinitrofluorobenzene sulfonic acid; D004139:Dinitrofluorobenzene