Periodontal Disease and Preterm Delivery: Influences of Campylobacter rectus Infection on Placental Innate Immunity Public Deposited

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  • June 7, 2019
  • Arce, Roger M.
    • Affiliation: School of Dentistry, Oral and Craniofacial Biomedicine PhD Program
  • Preterm delivery (PTD) is the major cause of neonatal mortality/ morbidity in the world. PTD pathogenesis can be initiated by multiple mechanisms; however inflammation is the most crucial step that leads to membrane weakening, placental rupture and early uterine contraction initiation. Maternal infections are believed to account for most of preterm delivery cases (25-40%), and uterine infections have been reported to be the leading cause of PTD. Vaginal microorganisms are capable of reaching the fetal membranes and inducing local proinflammatory response (chorioamnionitis) that ultimately results in PTD. Nonetheless, the treatment of symptomatic and/or asymptomatic uterine infections during pregnancy has revealed contradictory results in decreasing PTD rates. It has been speculated that other pathogens may come from different untreated focal infections in the body that reach the uterus through hematogenous dissemination and infect the maternal-fetal interface. In particular, Campylobacter rectus is a Gram negative anaerobe harbored in periodontitis-associated oral biofilms that has shown the competence to translocate to the fetoplacental unit and operate as a potential fetal infectious agent eliciting prematurity. Moreover, a number of clinical studies have found an association between periodontitis and preterm delivery. Maternal periodontitis has been found to be associated with increased risk for fetal exposure to periodontal pathogens in PTD cases. Yet, the underlying biological mechanisms sustaining preterm delivery onset after C. rectus infection remain largely unknown. This dissertation hypothesized that C rectus induces a placental innate inflammatory response mediated by Toll-like receptors (TLRs). Our experimental data on animal models have demonstrated C. rectus ability to disseminate from distant sites of infection, to induce a local placental inflammatory response along with a fetal intrauterine growth restriction phenotype, and to upregulate TLR-4 expression in placental trophoblasts after infection. The experimental results here presented demonstrated the importance of TLRs in mediating proinflammatory phenotype both in vitro (human trophoblastic cell line) and in vivo (murine) infection models in response to C. rectus infection. Taken together, the results here presented will elucidate in part the maternal/fetal biological mechanisms leading to PTD in humans, bringing new insights, theories and health policies into the preterm delivery field.
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  • ... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the School of Dentistry (Oral Biology)
  • Offenbacher, Steven

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