Heligmosomoides polygyrus induces TLR4 on murine mucosal T cells that produce TGFbeta after lipopolysaccharide stimulation.
Helminths are immune modulators that down-regulate colitis in inflammatory bowel disease. In animal models, intestinal bacteria drive colitis and in humans certain alleles of the LPS receptor protein TLR4 increase inflammatory bowel disease susceptibility. To understand helminthic immune modulation in the gut, we studied the influence of intestinal Heligmosomoides polygyrus colonization on LPS-induced lamina propria mononuclear cell (LPMC) cytokine responses in mice. LPS did not stimulate TGFbeta production from LPMC of uninfected mice. LPS strongly induced LPMC from worm-infected animals to secrete TGFbeta, but not TNF-alpha or IL-12. The TGFbeta derived from mucosal T cells. Helminth infection up-regulated TLR4 expression only in lamina propria T cells. LPMC from worm-infected TLR4 mutant animals did not respond to LPS, suggesting that LPS required TLR4 to stimulate TGFbeta secretion. Thus, during helminth infection, LPS challenge induces mucosal T cells to make TGFbeta through a TLR4-dependent process without promoting synthesis of proinflammatory cytokines.
Ince
M Nedim
MN
Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA. m-nedim-ince@uiowa.edu
Elliott
David E
DE
Setiawan
Tommy
T
Blum
Arthur
A
Metwali
Ahmed
A
Wang
Ying
Y
Urban
Joseph F
JF
Weinstock
Joel V
JV
D000818:Animals; D002478:Cells, Cultured; D015870:Gene Expression; D018928:Immunity, Mucosal; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009351:Nematospiroides dubius / Q000276:immunology / Q000472:pathogenicity*; D017206:Strongylida Infections / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis* / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D016212:Transforming Growth Factor beta