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-beta).


METHODS
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 kappa B (NFkappaB) 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 x 10(9) bacteria, while MyD88-KO and DKO animals were completely protected from delivery. Intrauterine fetal survival, maintenance of circulating progesterone levels, and nuclear translocation of NFkappaB were also dependent upon MyD88 but not TRIF. In contrast, induction of uterine interleukin (IL)-1beta and tumor necrosis factor alpha (TNF-alpha) depends upon actions of both MyD88 and TRIF.


CONCLUSIONS
E coli-induced preterm delivery in the mouse is completely dependent upon MyD88 but not TRIF.
Filipovich
Yana
Y
Department of Obstetrics and Gynecology, Evanston Northwestern Healthcare, Evanston, IL, USA.
Lu
Shi-Jiang
SJ
Akira
Shizuo
S
Hirsch
Emmet
E
D000818:Animals; D004926:Escherichia coli / Q000302:isolation & purification*; D004927:Escherichia coli Infections / Q000150:complications*; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000378:metabolism* / Q000382:microbiology; D047928:Premature Birth / Q000378:metabolism / Q000382:microbiology*; D011374:Progesterone / Q000378:metabolism; D012313:RNA / Q000737:chemistry / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D018709:Statistics, Nonparametric
C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D018123:Receptors, Interleukin; C476416:Ticam2 protein, mouse; D011374:Progesterone; D012313:RNA