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

Filipovich, Yana; Lu, Shi‐Jiang; Akira, Shizuo; Hirsch, Emmet

doi:10.1016/j.ajog.2008.08.038

Cited by 48 publications

(45 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the absence of this protein, a reduction of placental inflammation was observed, and fetal weight was therefore not affected. Consistent with this observation, using a model of preterm delivery induced by Escherichia coli infection, Filipovich and collaborators demonstrated that MyD88-deficient mice were protected from preterm delivery induced by bacterial infection compared to WT mice (53). Notably, although the MyD88-deficient mice were able to produce TNF-␣ in response to bacterial infection, the production of this cytokine was lower than in WT mice and was correlated with delayed TRIF signaling.…”

Section: Discussionsupporting

confidence: 50%

MyD88 Signaling Is Directly Involved in the Development of Murine Placental Malaria

et al. 2014

View full text Add to dashboard Cite

e Malaria is a widespread infectious disease caused by the parasite Plasmodium. During pregnancy, malaria infection leads to a range of complications that can affect both the mother and fetus, including stillbirth, infant mortality, and low birth weight. In this study, we utilized a mouse model of placental malaria (PM) infection to determine the importance of the protein MyD88 in the host immune response to Plasmodium during pregnancy. Initially, we demonstrated that Plasmodium berghei NK65GFP adhered to placental tissue via chondroitin sulfate A and induced PM in mice with a C57BL/6 genetic background. To evaluate the involvement of MyD88 in the pathology of PM, we performed a histopathological analysis of placentas obtained from MyD88 ؊/؊ and wild-type (WT) mice following infection on the 19th gestational day. Our data demonstrated that the detrimental placental alterations observed in the infected mice were correlated with the expression of MyD88. Moreover, in the absence of this protein, production of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-␣) was significantly reduced in the infected mice. More importantly, in contrast to fetuses from infected WT mice, which exhibited a reduction in body weight, the fetuses from infected MyD88 ؊/؊ mice did not display significant weight loss compared to their noninfected littermates. In addition, we observed a decrement of maternal care associated with malaria infection, which was attenuated in the MyD88-deficient mice. Collectively, the results of this study illustrate the pivotal importance of the MyD88 signaling pathway in the pathogenesis of placental malaria, thus presenting new possibilities for targeting MyD88 in therapeutic interventions.

show abstract

Section: Discussionsupporting

confidence: 50%

MyD88 Signaling Is Directly Involved in the Development of Murine Placental Malaria

et al. 2014

View full text Add to dashboard Cite

show abstract

“…In general, infections and infectious components trigger inflammation and preterm labor in mice; however, the type of stimuli used, as well as the timing and the dose administered, may determine the type of response generated and the tissues involved. For example, high-dose LPS delivered late in gestation (ED 14-17) induces preterm labor associated with placental and fetal inflammation (38)(39)(40), whereas heat-killed Escherichia coli induces preterm labor and uterine inflammation, without changes in placental or fetal cytokines (41,42). In contrast, infection with Ureaplasma late in gestation induces placental and fetal inflammation without preterm labor (43), whereas viral infection early in gestation (ED 8.5) triggers fetal and maternal splenic inflammation, without inducing placental inflammation or preterm labor (44).…”

Section: Discussionmentioning

confidence: 99%

Nod1 Activation by Bacterial iE-DAP Induces Maternal–Fetal Inflammation and Preterm Labor

Cardenas

Mulla

Myrtolli

et al. 2011

The Journal of Immunology

View full text Add to dashboard Cite

There is a strong association between infection and prematurity; however, the underlying mechanisms remain largely unknown. Nod1 and Nod2 are intracellular pattern recognition receptors that are activated by bacterial peptides and mediate innate immunity. We previously demonstrated that human first-trimester trophoblasts express Nod1 and Nod2, which trigger inflammation upon stimulation. This study sought to determine the expression and function of Nod1 and Nod2 in third-trimester trophoblasts, and to characterize the in vivo effects of Nod1 activation on pregnancy outcome. Human term placental tissues and isolated term trophoblast expressed Nod1, but not Nod2. Activation of Nod1 by its agonist, bacterial γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP), in term trophoblast cultures induced a proinflammatory cytokine profile, characterized by elevated levels of secreted IL-6, GRO-α, and MCP-1, when compared with the control. However, these cytokines were not upregulated in response to Nod2 stimulation with bacterial MDP. Administration of high-dose bacterial iE-DAP to pregnant C57BL/6J mice on embryonic day 14.5 triggered preterm delivery within 24 h. iE-DAP at a lower dose that did not induce prematurity, reduced fetal weight, altered the cytokine profile at the maternal–fetal interface, and induced fetal inflammation. Thus, functional Nod1 is expressed by trophoblast cells across gestation and may have a role in mediating infection-associated inflammation and prematurity. This study demonstrates that pattern recognition receptors, other than the TLRs, may be implicated or involved in infection-associated preterm labor.

show abstract

“…This proportion of preterm birth is less than that observed with RU486 (46) or LPS (47)(48)(49)(50) in which preterm delivery rates approach 100% possibly because fFN does not activate luteolysis or uterine contractility. Nonetheless, our experimental findings in vitro and in vivo indicate that fFN is not only a matrix molecule but is biologically active in vivo.…”

Section: Discussionmentioning

confidence: 73%

Fetal Fibronectin Signaling Induces Matrix Metalloproteases and Cyclooxygenase-2 (COX-2) in Amnion Cells and Preterm Birth in Mice

Mogami

Kishore

Shi

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:The function of fetal fibronectin (fFN) in the pathogenesis of preterm labor is not known. Results: fFN activates MMP-1, MMP-9, and COX-2 in mesenchymal cells and causes preterm labor in mice. Conclusion: fFN is biologically active and plays a significant role in the pathogenesis of preterm labor. Significance: Signaling of fFN in fetal membranes is important in the pathophysiology of premature preterm rupture of the membranes.

show abstract

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

Cited by 48 publications

References 39 publications

MyD88 Signaling Is Directly Involved in the Development of Murine Placental Malaria

MyD88 Signaling Is Directly Involved in the Development of Murine Placental Malaria

Nod1 Activation by Bacterial iE-DAP Induces Maternal–Fetal Inflammation and Preterm Labor

Fetal Fibronectin Signaling Induces Matrix Metalloproteases and Cyclooxygenase-2 (COX-2) in Amnion Cells and Preterm Birth in Mice

Contact Info

Product

Resources

About