Toll-like receptor 4 mediates intrauterine growth restriction after systemic Campylobacter rectus infection in mice

R. M. Arce, K. M. Caron, S. P. Barros, S. Offenbacher

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Campylobacter rectus is associated with fetal exposure and low birthweight in humans. C. rectus also invades placental tissues and induces fetal intrauterine growth restriction (IUGR) in mice, along with overexpression of Toll-like receptors (TLR4), suggesting that TLR4 may mediate placental immunity and IUGR in mice. To test this hypothesis we examined the effect of in vitro TLR4 neutralization on trophoblastic proinflammatory activity and studied the IUGR phenotype in a congenic TLR4-mutant mouse strain after in vivo C. rectus infection. Human trophoblasts were pretreated with TLR4 neutralizing antibodies and infected with C. rectus; proinflammatory cytokine production was assessed by cytokine multiplex assays. Neutralizing TLR4 antibodies significantly impaired the production of proinflammatory cytokines in trophoblastic cells after infection in a dose-dependent manner. We used a subcutaneous chamber model to provide a C. rectus challenge in BALB/cAnPt (TLR4Lps-d) and wild-type (WT) females. Females were mated with WT or TLR4Lps-d males once/week; pregnant mice were infected at (E)7.5 and sacrificed at (E)16.5 to establish IUGR phenotypes. Maternal C. rectus infection significantly decreased fetal weight/length in infected WT when compared with sham WT controls (P<0.05, analysis of variance). However, infected TLR4Lps-d-/- mice did not show statistically significant differences in fetal weight and length when compared with WT controls (P>0.05). Furthermore, heterozygous TLR4Lps-d+/- fetuses showed IUGR phenotype rescue. We conclude that TLR4 is an important mediator of trophoblastic proinflammatory responses and TLR4-deficient fetuses do not develop IUGR phenotypes after C. rectus infection, suggesting that placental cytokine activation is likely to be mediated by TLR4 during low birthweight/preterm birth pathogenesis.

Original languageEnglish (US)
Pages (from-to)373-381
Number of pages9
JournalMolecular Oral Microbiology
Issue number5
StatePublished - Oct 2012
Externally publishedYes


  • Animal models
  • Campylobacter rectus
  • Fetal growth restriction
  • Mice
  • Periodontitis
  • Preterm delivery
  • Toll-like receptors

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Dentistry(all)
  • Microbiology (medical)


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