Ureaplasma-Driven Neonatal Neuroinflammation: Novel Insights from an Ovine Model

Christine Silwedel*, Matthias C Hütten, Christian P Speer, Christoph Härtel, Axel Haarmann, Birgit Henrich, Maud P M Tijssen, Abdullah Ahmed Alnakhli, Owen B Spiller, Nicolas Schlegel, Silvia Seidenspinner, Boris W Kramer, Kirsten Glaser

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Ureaplasma species (spp.) are considered commensals of the adult genitourinary tract, but have been associated with chorioamnionitis, preterm birth, and invasive infections in neonates, including meningitis. Data on mechanisms involved in Ureaplasma-driven neuroinflammation are scarce. The present study addressed brain inflammatory responses in preterm lambs exposed to Ureaplasma parvum (UP) in utero. 7 days after intra-amniotic injection of UP (n = 10) or saline (n = 11), lambs were surgically delivered at gestational day 128-129. Expression of inflammatory markers was assessed in different brain regions using qRT-PCR and in cerebrospinal fluid (CSF) by multiplex immunoassay. CSF was analyzed for UP presence using ureB-based real-time PCR, and MRI scans documented cerebral white matter area and cortical folding. Cerebral tissue levels of atypical chemokine receptor (ACKR) 3, caspases 1-like, 2, 7, and C-X-C chemokine receptor (CXCR) 4 mRNA, as well as CSF interleukin-8 protein concentrations were significantly increased in UP-exposed lambs. UP presence in CSF was confirmed in one animal. Cortical folding and white matter area did not differ among groups. The present study confirms a role of caspases and the transmembrane receptors ACKR3 and CXCR4 in Ureaplasma-driven neuroinflammation. Enhanced caspase 1-like, 2, and 7 expression may reflect cell death. Increased ACKR3 and CXCR4 expression has been associated with inflammatory central nervous system (CNS) diseases and impaired blood-brain barrier function. According to these data and previous in vitro findings from our group, we speculate that Ureaplasma-induced caspase and receptor responses affect CNS barrier properties and thus facilitate neuroinflammation.

Original languageEnglish
Pages (from-to)785-795
Number of pages11
JournalCellular and Molecular Neurobiology
Issue number2
Early online date25 Mar 2022
Publication statusPublished - Mar 2023


  • Animal model
  • CNS Integrity
  • Immaturity
  • LUNG
  • Neonatal meningitis
  • Preterm birth
  • Ureaplasma parvum


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