Helicobacter infection alters MyD88 and Trif signalling in response to intestinal ischaemia-reperfusion.
Ischaemia-reperfusion-induced intestinal injury requires both Toll-like receptor 4 (TLR4) signalling through myeloid differentiation primary response gene (88) (MyD88) and complement activation. As a common Gram-negative intestinal pathogen, Helicobacter hepaticus signals through TLR4 and upregulates the complement inhibitor, decay accelerating factor (DAF; CD55). Since ischaemia-reperfusion (IR) injury is complement dependent, we hypothesized that Helicobacter infection may alter IR-induced intestinal damage. Infection increased DAF transcription and subsequently decreased complement activation in response to IR without altering intestinal damage in wild-type mice. Ischaemia-reperfusion induced similar levels of DAF mRNA expression in uninfected wild-type, MyD88(-/-) or TIR-domain-containing adaptor-inducing interferon-β (Trif)-deficient mice. However, during infection, IR-induced DAF transcription was significantly attenuated in Trif-deficient mice. Likewise, IR-induced intestinal damage, complement component 3 deposition and prostaglandin E(2) production were attenuated in Helicobacter-infected, Trif-deficient but not MyD88(-/-) mice. While infection attenuated IR-induced cytokine production in wild-type and MyD88(-/-) mice, there was no further decrease in Trif-deficient mice. These data indicate distinct roles for MyD88 and Trif in IR-induced inflammation and suggest that chronic, undetected infections, such as Helicobacter, alter the use of the adaptor proteins to induce damage.
Kansas State University, Division of Biology, Manhattan, KS 66506, USA.
Sara M
SM
Hoffman
Hua
H
Wang
Michael R
MR
Pope
Sherry D
SD
Fleming
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000818:Animals; D016481:Helicobacter Infections / Q000378:metabolism*; D007410:Intestinal Diseases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism*; D015398:Signal Transduction
D033942:Adaptor Proteins, Vesicular Transport; D053594:Myeloid Differentiation Factor 88; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse