TY  - JOUR
A1  - Silwedel, Christine
A1  - Speer, Christian P.
A1  - Haarmann, Axel
A1  - Fehrholz, Markus
A1  - Claus, Heike
A1  - Schlegel, Nicolas
A1  - Glaser, Kirsten
T1  - Ureaplasma species modulate cytokine and chemokine responses in human brain microvascular endothelial cells
JF  - International Journal of Molecular Science
N2  - 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.
KW  - Ureaplasma urealyticum
KW  - Ureaplasma parvum
KW  - neuroinflammation
KW  - meningitis
KW  - blood–brain barrier
KW  - HBMEC
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201848
SN  - 1422-0067
VL  - 20
IS  - 14
ER  - 
TY  - JOUR
A1  - Glaser, Kirsten
A1  - Gradzka-Luczewska, Anna
A1  - Szymankiewicz-Breborowicz, Marta
A1  - Kawczynska-Leda, Natalia
A1  - Henrich, Birgit
A1  - Waaga-Gasser, Ana Maria
A1  - Speer, Christian P.
T1  - Perinatal ureaplasma exposure is associated with increased risk of late onset sepsis and imbalanced inflammation in preterm infants and may add to lung injury
JF  - Frontiers in Cellular and Infection Microbiology
N2  - Background: Controversy remains concerning the impact of Ureaplasma on preterm neonatal morbidity.

Methods: Prospective single-center study in very low birth weight infants <30 weeks' gestation. Cord blood and initial nasopharyngeal swabs were screened for Ureaplasma parvum and U. urealyticum using culture technique and polymerase chain reaction. Neonatal outcomes were followed until death or discharge. Multi-analyte immunoassay provided cord blood levels of inflammatory markers. Using multivariate regression analyses, perinatal Ureaplasma exposure was evaluated as risk factor for the development of bronchopulmonary dysplasia (BPD), other neonatal morbidities until discharge and systemic inflammation at admission.

Results: 40/103 (39%) infants were positive for Ureaplasma in one or both specimens, with U. parvum being the predominant species. While exposure to Ureaplasma alone was not associated with BPD, we found an increased risk of BPD in Ureaplasma-positive infants ventilated ≥5 days (OR 1.64; 95% CI 0.12–22.98; p = 0.009). Presence of Ureaplasma was associated with a 7-fold risk of late onset sepsis (LOS) (95% CI 1.80–27.39; p = 0.014). Moreover, Ureaplasma-positive infants had higher I/T ratios (b 0.39; 95% CI 0.08–0.71; p = 0.014), increased levels of interleukin (IL)-17 (b 0.16; 95% CI 0.02–0.30; p = 0.025) and matrix metalloproteinase 8 (b 0.77; 95% CI 0.10–1.44; p = 0.020), decreased levels of IL-10 (b −0.77; 95% CI −1.58 to −0.01; p = 0.043) and increased ratios of Tumor necrosis factor-α, IL-8, and IL-17 to anti-inflammatory IL-10 (p = 0.003, p = 0.012, p < 0.001).

Conclusions: Positive Ureaplasma screening was not associated with BPD. However, exposure contributed to BPD in infants ventilated ≥5 days and conferred an increased risk of LOS and imbalanced inflammatory cytokine responses.
KW  - Ureaplasma parvum
KW  - Ureaplasma urealyticum
KW  - preterm infants
KW  - VLBW
KW  - bronchopulmonary dysplasia
KW  - late onset sepsis
KW  - neonatal outcome
KW  - inflammation
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201270
VL  - 9
IS  - 68
ER  -