TY  - JOUR
A1  - Kim, Brandon J.
A1  - Shusta, Eric V.
A1  - Doran, Kelly S.
T1  - Past and current perspectives in modeling bacteria and blood–brain barrier interactions
JF  - Frontiers in Microbiology
N2  - The central nervous system (CNS) barriers are highly specialized cellular barriers that promote brain homeostasis while restricting pathogen and toxin entry. The primary cellular constituent regulating pathogen entry in most of these brain barriers is the brain endothelial cell (BEC) that exhibits properties that allow for tight regulation of CNS entry. Bacterial meningoencephalitis is a serious infection of the CNS and occurs when bacteria can cross specialized brain barriers and cause inflammation. Models have been developed to understand the bacterial – BEC interaction that lead to pathogen crossing into the CNS, however, these have been met with challenges due to these highly specialized BEC phenotypes. This perspective provides a brief overview and outlook of the in vivo and in vitro models currently being used to study bacterial brain penetration, and opinion on improved models for the future.
KW  - bacteria
KW  - blood–brain barrier
KW  - meningitis
KW  - stem cells
KW  - brain endothelial cell
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201766
VL  - 10
IS  - 1336
ER  - 
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  -