More than just inflammation: Ureaplasma species induce apoptosis in human brain microvascular endothelial cells | Journal of Neuroinflammation | Full Text

More than just inflammation: Ureaplasma species induce apoptosis in human brain microvascular endothelial cells | Journal of Neuroinflammation | Full Text



Journal of Neuroinflammation

More than just inflammation: Ureaplasma species induce apoptosis in human brain microvascular endothelial cells

• Christine SilwedelEmail authorView ORCID ID profile,
• Axel Haarmann,
• Markus Fehrholz,
• Heike Claus,
• Christian P. Speer and
• Kirsten Glaser

Journal of Neuroinflammation201916:38

https://doi.org/10.1186/s12974-019-1413-8

©  The Author(s). 2019

• Received: 30 October 2018
• Accepted: 24 January 2019
• Published: 14 February 2019

Abstract

Background

Ureaplasma species (spp.) are commonly regarded as low-virulent commensals but may cause invasive diseases in immunocompromised adults and in neonates, including neonatal meningitis. The interactions of Ureaplasma spp. with host defense mechanisms are poorly understood. This study addressed Ureaplasma-driven cell death, concentrating on apoptosis as well as inflammatory cell death.

Methods

Human brain microvascular endothelial cells (HBMEC) were exposed to Ureaplasma (U.) urealyticum serovar 8 (Uu8) and U. parvum serovar 3 (Up3). Resulting numbers of dead cells as well as mRNA levels and enzyme activity of key agents in programmed cell death were assessed by flow cytometry, RNA sequencing, and qRT-PCR, respectively. xCELLigence data were used for real-time monitoring of changes in cell adhesion properties.

Results

Both Ureaplasma isolates induced cell death (p < 0.05, vs. broth). Furthermore, Ureaplasma spp. enhanced mRNA levels for genes in apoptosis, including caspase 3 (Up3 p < 0.05, vs. broth), caspase 7 (p < 0.01), and caspase 9 (Up3 p < 0.01). Caspase 3 activity was increased upon Uu8 exposure (p < 0.01). Vice versa, Ureaplasma isolates downregulated mRNA levels for proteins involved in inflammatory cell death, namely caspase 1 (Uu8 p < 0.01, Up3 p < 0.001), caspase 4 (Uu8 p < 0.05, Up3 p < 0.01), NOD-like receptor pyrin domain-containing 3 (Uu8 p < 0.05), and receptor-interacting protein kinase 3 (p < 0.05).

Conclusions

By inducing apoptosis in HBMEC as main constituents of the blood-brain barrier, Ureaplasma spp. may provoke barrier breakdown. Simultaneous suppression of inflammatory cell death may additionally attenuate host defense strategies. Ultimate consequence could be invasive and long-term CNS infections by Ureaplasma spp.

Keywords

• Ureaplasma urealyticum
• Ureaplasma parvum
• Neuroinflammation
• Meningitis
• Caspase
• Apoptosis
• HBMEC