Characterization of the invasive and inflammatory traits of oral Campylobacter rectus in a murine model of fetoplacental growth restriction and in trophoblast cultures

Abstract

Campylobacter species (C. jejuni, C. fetus) are enteric abortifacient bacteria in humans and ungulates. Campylobacter rectus is a periodontal pathogen associated with human fetal exposure and adverse pregnancy outcomes including preterm delivery. Experiments in pregnant mice have demonstrated that C. rectus can translocate from a distant site of infection to the placenta to induce fetal growth restriction and impair placental development. However, placental tissues from human, small-forgestational age deliveries have not been reported to harbor C. rectus despite evidence of maternal infection and fetal exposure by fetal IgM response. This investigation examined the temporal relationship between the placental translocation of C. rectus and the effects on fetal growth in mice. BALB/c mice were infected at gestational day E7.5 to examine placental translocation of C. rectus by immunohistology. C. rectus significantly decreased fetoplacental weight at E14.5 and at E16.5. C. rectus was detected in 63% of placentas at E14.5, but not at E16.5. In in vitro trophoblast invasion assays, C. rectus was able to effectively invade human trophoblasts (BeWo) but not murine trophoblasts (SM9-1), and showed a trend for more invasiveness than C. jejuni. C. rectus challenge significantly upregulated both mRNA and protein levels of IL-6 and TNFα in a dose-dependent manner in human trophoblasts, but did not increase cytokine expression in murine cells, suggesting a correlation between invasion and cytokine activation. In conclusion, the trophoblast-invasive trait of C. rectus that appears limited to human trophoblasts may play a role in facilitating bacterial translocation and placental inflammation during early gestation.

Identification and Characterization of an Invasion Antigen B Gene from the Oral Pathogen Campylobacter rectus

“…However, the discovery of C. rectus 314 CiaB in this study, taken together with the observed cell invasion by C. rectus, suggests that CiaB may play a role in this phenotype [23]. Future studies aim to verify the function of CiaB biochemically.…”

“…Interestingly, C. rectus 314 CiaB also appears to lack a signal peptide ( Table 3). As previously mentioned, C. rectus 314, like C. jejuni, has been shown to invade eukaryotic cells, including placental trophoblasts [23]. Invasion of placental trophoblasts is important, as previous studies have suggested that C. rectus plays a significant role in the preterm labors of mothers with periodontitis [10,11] and has the ability to translocate to the placenta, from a distant site of infection, in mouse models of periodontitis.…”

“…In addition, ciaB genes have been identified from additional campylobacters including Campylobacter lari, Campylobacter coli, and Campylobacter upsaliensis [21,22]. Given the conservation of ciaB, and a recent study showing C. rectus 314 can invade host cells [23], we hypothesized that the C. rectus 314 contains a ciaB gene. In this study, a combination of PCR, PCR-walking, reverse transcriptase PCR, and in silico tools were used to characterize a ciaB gene (Cr-ciaB) from C. rectus 314.…”

“…In this study, a combination of PCR, PCR-walking, reverse transcriptase PCR, and in silico tools were used to characterize a ciaB gene (Cr-ciaB) from C. rectus 314. The identification of C. rectus CiaB suggests that CiaB might contribute to the pathogenesis of C. rectus during host cell invasion [23]; and raises the possibility of developing novel periodontal therapeutics that disrupt CiaB functionality.…”

Campylobacter

“…In a recent study, Arce et al determined the in vitro ability of C. rectus to invade human as well as murine trophoblast cells [198]. This showed for the first time that in vitro, C. rectus could invade human but not murine trophoblastic cells.…”