Heligmosomoides polygyrus promotes regulatory T-cell cytokine production in the murine normal distal intestine.
Helminths down-regulate inflammation and may prevent development of several autoimmune illnesses, such as inflammatory bowel disease. We determined if exposure to the duodenal helminth Heligmosomoides polygyrus establishes cytokine pathways in the distal intestine that may protect from intestinal inflammation. Mice received 200 H. polygyrus larvae and were studied 2 weeks later. Lamina propria mononuclear cells (LPMC) were isolated from the terminal ileum for analysis and in vitro experiments. Mice with H. polygyrus were resistant to trinitrobenzenesulfonic acid (TNBS)-induced colitis, a Th1 cytokine-dependent inflammation. Heligmosomoides polygyrus did not change the normal microscopic appearance of the terminal ileum and colon and minimally affected LPMC composition. However, colonization altered LPMC cytokine profiles, blocking gamma interferon (IFN-gamma) and interleukin 12 (IL-12) p40 release but promoting IL-4, IL-5, IL-13, and IL-10 secretion. IL-10 blockade in vitro with anti-IL-10 receptor (IL-10R) monoclonal antibody restored LPMC IFN-gamma and IL-12 p40 secretion. IL-10 blockade in vivo worsened TNBS colitis in H. polygyrus-colonized mice. Lamina propria CD4(+) T cells isolated from colonized mice inhibited IFN-gamma production by splenic T cells from worm-free mice. This inhibition did not require cell contact and was dependent on IL-10. Heligmosomoides polygyrus colonization inhibits Th1 and promotes Th2 and regulatory cytokine production in distant intestinal regions without changing histology or LPMC composition. IL-10 is particularly important for limiting the Th1 response. The T-cell origin of these cytokines demonstrates mucosal regulatory T-cell induction.
Setiawan
Tommy
T
Division of Gastroenterology (4611 JCP), University of Iowa Hospital and Clinics, 200 Hawkins Drive, Iowa City, IA 52242-1009, USA.
Metwali
Ahmed
A
Blum
Arthur M
AM
Ince
M Nedim
MN
Urban
Joseph F
JF
Elliott
David E
DE
Weinstock
Joel V
JV
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D007420:Intestine, Large / Q000276:immunology / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009351:Nematospiroides dubius / Q000276:immunology*; D017206:Strongylida Infections / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology
D016207:Cytokines