Cutting edge:: Heligmosomoides polygyrus induces TLR4 on murine mucosal T cells that produce TGFβ 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 TGF beta production from LPMC of uninfected mice. LPS strongly induced LPMC from worm-infected animals to secrete TGF beta, but not TNF-alpha or IL-12. The TGF beta derivedfrom 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 TGF beta secretion. Thus, during helminth infection, LPS challenge induces mucosal T cells to make TGF beta through a TLR4-dependent process without promoting synthesis of proinflammatory cytokines.