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The adaptor protein MyD88 is essential for E coli–induced preterm delivery in mice

      Objective

      We used a mouse model of infection-induced preterm delivery to examine the roles of 2 adaptor proteins with central functions in Toll-like receptor signaling: MyD88 (myeloid differentiation primary-response gene 88) and TRIF (Toll/IL-1 receptor (TIR)-domain-containing adaptor protein-inducing IFN-β).

      Study Design

      Mice deficient (KO) for MyD88, TRIF, both (DKO) or neither (WT) were inoculated into the uterus with killed Escherichia coli. Delivery outcomes, fetal status, serum progesterone, and nuclear translocation of the transcription factor nuclear factor κ B (NFκB) were determined.

      Results

      Preterm birth (delivery in less than 48 hours) occurred in WT and TRIF-KO animals in a dose-dependent fashion, reaching 100% with 5-10 × 109 bacteria, while MyD88-KO and DKO animals were completely protected from delivery. Intrauterine fetal survival, maintenance of circulating progesterone levels, and nuclear translocation of NFκB were also dependent upon MyD88 but not TRIF. In contrast, induction of uterine interleukin (IL)-1β and tumor necrosis factor alpha (TNF-α) depends upon actions of both MyD88 and TRIF.

      Conclusion

      E coli–induced preterm delivery in the mouse is completely dependent upon MyD88 but not TRIF.

      Key words

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