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

Area of Science:

• Microbiology
• Immunology
• Neuroscience

Background:

• Ureaplasma species are common genitourinary tract colonizers, often viewed as low-virulence commensals.
• However, intraamniotic Ureaplasma infections are linked to preterm birth, and neonatal Ureaplasma infections can cause sepsis, pneumonia, and meningitis.
• In vitro data on Ureaplasma's impact on immune mechanisms are limited.

Purpose of the Study:

• To investigate the cytokine and chemokine responses of human brain microvascular endothelial cells (HBMEC) upon exposure to Ureaplasma urealyticum and U. parvum.
• To analyze the effects of Ureaplasma on both native and lipopolysaccharide (LPS)-co-stimulated HBMEC.

Main Methods:

• Utilized quantitative reverse transcription PCR (qRT-PCR) and RNA sequencing to assess gene expression.
• Employed multi-analyte immunoassay and flow cytometry to measure protein secretion and cell responses.
• Exposed native and LPS-co-stimulated HBMEC to Ureaplasma species.

Main Results:

• Ureaplasma exposure reduced monocyte chemoattractant protein (MCP)-3 mRNA in native HBMEC.
• In LPS-co-stimulated HBMEC, Ureaplasma attenuated LPS-induced mRNA expression for C-X-C chemokine ligand 5, MCP-1, and MCP-3.
• Ureaplasma mitigated LPS-driven interleukin (IL)-1α and IL-8 protein secretion and IL-8 mRNA levels, while increasing C-X-C chemokine receptor 4 mRNA.

Conclusions:

• Ureaplasma species possess immunomodulatory capabilities that affect brain endothelial cells.
• These effects may facilitate chronic colonization by Ureaplasma.
• The findings suggest a potential role for Ureaplasma in promoting long-term neuroinflammation.