<i>Ureaplasma</i> Species Modulate Cytokine and Chemokine Responses in Human Brain Microvascular Endothelial Cells

• Main Authors: Christine Silwedel, Christian P. Speer, Axel Haarmann, Markus Fehrholz, Heike Claus, Nicolas Schlegel, Kirsten Glaser
• Format: Article
• Language: English
• Published: MDPI AG 2019-07-01
• Series: International Journal of Molecular Sciences
• Subjects: <i>Ureaplasma urealyticum</i>; <i>Ureaplasma parvum</i>; neuroinflammation; meningitis; blood–brain barrier; HBMEC
• Online Access: https://www.mdpi.com/1422-0067/20/14/3583

<i>Ureaplasma</i> species are common colonizers of the adult genitourinary tract and often considered as low-virulence commensals. Intraamniotic <i>Ureaplasma</i> infections, however, facilitate chorioamnionitis and preterm birth, and cases of <i>Ureaplasma</i>-induced neonatal sepsis, pneumonia, and meningitis raise a growing awareness of their clinical relevance. In vitro studies are scarce but demonstrate distinct <i>Ureaplasma</i>-driven impacts on immune mechanisms. The current study addressed cytokine and chemokine responses upon exposure of native or lipopolysaccharide (LPS) co-stimulated human brain microvascular endothelial cells (HBMEC) to <i>Ureaplasma urealyticum</i> or <i>U. parvum</i>, using qRT-PCR, RNA sequencing, multi-analyte immunoassay, and flow cytometry. <i>Ureaplasma</i> exposure in native HBMEC reduced monocyte chemoattractant protein (MCP)-3 mRNA expression (<i>p</i> &lt; 0.01, vs. broth). In co-stimulated HBMEC, <i>Ureaplasma</i> spp. attenuated LPS-evoked mRNA responses for C-X-C chemokine ligand 5, MCP-1, and MCP-3 (<i>p</i> &lt; 0.05, vs. LPS) and mitigated LPS-driven interleukin (IL)-1&#945; protein secretion, as well as IL-8 mRNA and protein responses (<i>p</i> &lt; 0.05). Furthermore, <i>Ureaplasma</i> isolates increased C-X-C chemokine receptor 4 mRNA levels in native and LPS co-stimulated HBMEC (<i>p</i> &lt; 0.05). The presented results may imply immunomodulatory capacities of <i>Ureaplasma</i> spp. which may ultimately promote chronic colonization and long-term neuroinflammation.