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Open AccessArticle

Ureaplasma Species Modulate Cytokine and Chemokine Responses in Human Brain Microvascular Endothelial Cells

1
University Children’s Hospital, University of Wuerzburg, Josef-Schneider-Str. 2, 97080 Wuerzburg, Germany
2
Department of Neurology, University of Wuerzburg, Josef-Schneider-Str. 11, 97080 Wuerzburg, Germany
3
Institute for Hygiene and Microbiology, University of Wuerzburg, Josef-Schneider-Str. 2, 97080 Wuerzburg, Germany
4
Department of Surgery I, University of Wuerzburg, Oberduerrbacherstr. 6, 97080 Wuerzburg, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(14), 3583; https://doi.org/10.3390/ijms20143583
Received: 28 May 2019 / Revised: 11 July 2019 / Accepted: 18 July 2019 / Published: 22 July 2019
(This article belongs to the Special Issue Small Vessel Disease: A Whole Brain Disease)
Ureaplasma species are common colonizers of the adult genitourinary tract and often considered as low-virulence commensals. Intraamniotic Ureaplasma infections, however, facilitate chorioamnionitis and preterm birth, and cases of Ureaplasma-induced neonatal sepsis, pneumonia, and meningitis raise a growing awareness of their clinical relevance. In vitro studies are scarce but demonstrate distinct Ureaplasma-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 Ureaplasma urealyticum or U. parvum, using qRT-PCR, RNA sequencing, multi-analyte immunoassay, and flow cytometry. Ureaplasma exposure in native HBMEC reduced monocyte chemoattractant protein (MCP)-3 mRNA expression (p < 0.01, vs. broth). In co-stimulated HBMEC, Ureaplasma spp. attenuated LPS-evoked mRNA responses for C-X-C chemokine ligand 5, MCP-1, and MCP-3 (p < 0.05, vs. LPS) and mitigated LPS-driven interleukin (IL)-1α protein secretion, as well as IL-8 mRNA and protein responses (p < 0.05). Furthermore, Ureaplasma isolates increased C-X-C chemokine receptor 4 mRNA levels in native and LPS co-stimulated HBMEC (p < 0.05). The presented results may imply immunomodulatory capacities of Ureaplasma spp. which may ultimately promote chronic colonization and long-term neuroinflammation. View Full-Text
Keywords: Ureaplasma urealyticum; Ureaplasma parvum; neuroinflammation; meningitis; blood–brain barrier; HBMEC Ureaplasma urealyticum; Ureaplasma parvum; neuroinflammation; meningitis; blood–brain barrier; HBMEC
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Silwedel, C.; Speer, C.P.; Haarmann, A.; Fehrholz, M.; Claus, H.; Schlegel, N.; Glaser, K. Ureaplasma Species Modulate Cytokine and Chemokine Responses in Human Brain Microvascular Endothelial Cells. Int. J. Mol. Sci. 2019, 20, 3583.

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