Colonization with Heligmosomoides polygyrus suppresses mucosal IL-17 production.
Helminth exposure appears to protect hosts from inappropriate inflammatory responses, such as those causing inflammatory bowel disease. A recently identified, strongly proinflammatory limb of the immune response is characterized by T cell IL-17 production. Many autoimmune type inflammatory diseases are associated with IL-17 release. Because helminths protect from these diseases, we examined IL-17 production in helminth-colonized mice. We colonized mice with Heligmosomoides polygyrus, an intestinal helminth, and analyzed IL-17 production by lamina propria mononuclear cells (LPMC) and mesenteric lymph node (MLN) cells. Colonization with H. polygyrus reduces IL-17A mRNA by MLN cells and inhibits IL-17 production by cultured LPMC and MLN cells. Helminth exposure augments IL-4 and IL-10 production. Blocking both IL-4 and IL-10, but not IL-10 alone, restores IL-17 production in vitro. Colonization of colitic IL-10-deficient mice with H. polygyrus suppresses LPMC IL-17 production and improves colitis. Ab-mediated blockade of IL-17 improves colitis in IL-10-deficient mice. Thus, helminth-associated inhibition of IL-17 production is most likely an important mechanism mediating protection from inappropriate intestinal inflammation.
Elliott
David E
DE
Department of Veterans Affairs Medical Center, Iowa City, IA 52246, USA. david-elliott@uiowa.edu
Metwali
Ahmed
A
Leung
John
J
Setiawan
Tommy
T
Blum
Arthur M
AM
Ince
M Nedim
MN
Bazzone
Lindsey E
LE
Stadecker
Miguel J
MJ
Urban
Joseph F
JF
Weinstock
Joel V
JV
D000818:Animals; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D007108:Immune Tolerance; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000378:metabolism; D015847:Interleukin-4 / Q000502:physiology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D008643:Mesentery; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009351:Nematospiroides dubius / Q000254:growth & development* / Q000276:immunology*; D017206:Strongylida Infections / Q000276:immunology / Q000378:metabolism / Q000469:parasitology
D020381:Interleukin-17; D015847:Interleukin-4