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.