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14: Extravillous trophoblasts within the placental basal plate serve as a protected niche for intracellular bacterial reservoirs: potential new etiology for preterm birth

      Objective

      Infection and inflammation are important mechanisms contributing to Preterm birth (PTB). However, the mechanism by which pathogens infect and induce pathological change during pregnancy remains unknown as does the contribution of latent and chronic infection. Antibiotic treatment is relatively ineffective for preventing PTB suggesting that the putative infectious organisms may be ‘hidden’ within the tissue. Our central hypothesis is that one cause of PTB is that bacterial pathogens establish clinically occult reservoirs in fetal extravillous trophoblasts (EVTs) on the maternal side of the placenta (basal plate).

      Study Design

      Placental basal plate biopsies were collected from n=200 women with PTB <37 weeks and controls ≥37 weeks, stained with the Brown-Hopps modification of the Gram-stain and examined for intracellular bacteria. To explore the mechanisms underlying formation of intracellular bacterial reservoirs, ex vivo human basal plate explants were developed and infected with Gram-negative. (Uropathogenic E. coli, UPEC) and Gram-positive (Listeria monocytogenes) pathogens.

      Results

      Intracellular bacteria were documented in over a third of preterm placentas and were exclusively localized to fetal EVTs (Figure 1A-B). We show that both UPEC and Listeria invade into HLA-G+ EVTs embedded within the basal plate. Bacteria appear to hone directly to fetal EVTs and not maternal stromal cells. Interestingly, UPEC appear to form biofilm-like clusters in EVTs whereas Listeria remain as single organisms (Figure 1C-D).
      Figure thumbnail grr5
      A and B, Intracellular bacteria in EVTs in placental basal plate. C and D, UPEC and Listeria invading and surviving intracellularly within EVTs in placental basal plate explants (HLA-G+, red).

      Conclusion

      Our work has thus demonstrated that EVTs are highly susceptible to bacterial invasion and colonization likely due to their unique immune-privileged status. We show that Gram positive and negative bacteria may use different mechanisms to persist. We posit that such reservoirs persisting within EVTs in the basal plate could re-emerge and predispose to adverse pregnancy outcomes such as PTB.