Characterization of the immuno-regulatory response to the tapeworm Hymenolepis diminuta in the non-permissive mouse host.

Abstract

UNLABELLED:

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.

IN CONCLUSION:

(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.

• Authors: Robin Persaud, Arthur Wang, Colin Reardon, Derek M McKay
• Journal: International journal for parasitology (Int J Parasitol) Vol. 37 Issue 3-4 Pg. 393-403 (Mar 2007) ISSN: 0020-7519 [Print] England
• PMID: 17092505 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Forkhead Transcription Factors
• Foxp3 protein, mouse
• RNA, Messenger
• Interleukin-10
• 2,4-dinitrofluorobenzene sulfonic acid
• Dinitrofluorobenzene

Topics

• Animals
• CD4-Positive T-Lymphocytes (immunology)
• Colitis (chemically induced, immunology, prevention & control)
• Cytokines (biosynthesis, genetics)
• Dinitrofluorobenzene (analogs & derivatives)
• Disease Susceptibility
• Forkhead Transcription Factors (biosynthesis, genetics)
• Gene Expression Regulation (immunology)
• Host-Parasite Interactions (immunology)
• Hymenolepiasis (immunology)
• Hymenolepis diminuta (immunology, physiology)
• Interleukin-10 (biosynthesis, genetics)
• Intestinal Mucosa (immunology, parasitology)
• Ion Transport
• Jejunum (immunology, parasitology)
• Macrophage Activation (immunology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• RNA, Messenger (genetics)
• T-Lymphocytes, Regulatory (immunology)