Background: Filamentous haemagglutinin (FHA) of Bordetella pertussis subverts host immune responses by inhibiting interleukin (IL)12 and enhancing IL10 production by macrophages and dendritic cells, and promoting the induction of regulatory T cells.
Hypothesis: Injection of FHA would ameliorate disease in a T cell-dependent model of colitis via the induction of anti-inflammatory cytokines and regulatory T cells.
Methods: Colitis was induced by injection of CD4CD45RBhigh naive T cells into severe combined immunodeficient (SCID) mice. Mice were treated with four subcutaneous injections of FHA or buffer alone.
Results: Parenteral injection of FHA stimulated IL10 and/or transforming growth factor β production in local and mesenteric lymph nodes and Peyer’s patches of mice 2–6 h after administration. Compared with phosphate-buffered saline-treated mice, FHA-treated SCID mice had significantly (p<0.01) less weight loss, lower colon weight, less colon shrinkage and reduced inflammatory lesions. The therapeutic effect of FHA was associated with enhanced IL10 and reduced type 1 and type 2 T helper cytokine production by spleen cells. Finally, FHA also attenuated the symptoms of colitis in SCID mice transferred with CD4CD45RBhigh T cells from IL10-deficient mice.
Conclusions: Our finding shows that FHA suppresses type 1 T helper and pro-inflammatory cytokines, and ameliorates disease activity in a chronic T cell-dependent model of colitis, an effect that was not dependent on IL10 production by T cells, but was associated with induction of anti-inflammatory cytokines in vivo. Having already been used as a pertussis vaccine component in children, FHA is a promising candidate for clinical testing in patients with Crohn’s disease.
- FHA, filamentous haemagglutinin
- IFN, interferon
- IL10−/−, interleukin-10-defective
- PBS, phosphate-buffered-saline
- Th1, type 1 T helper cell
- TGF, transforming growth factor
- TLR, Toll-like receptor
- TNF, tumour necrosis factor
- SCID, severe combined immunodeficient
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