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The role of plasminogen activator inhibitor-2 in pneumococcal meningitis. / Teske, Nina C.; Engelen-Lee, Joo-Yeon; Dyckhoff-Shen, Susanne et al.

In: Acta neuropathologica communications, Vol. 10, No. 1, 155, 01.12.2022.

Research output: Contribution to journalArticleAcademicpeer-review

Harvard

Teske, NC, Engelen-Lee, J-Y, Dyckhoff-Shen, S, Pfister, H-W, Klein, M, van de Beek, D, Kirschning, CK, Koedel, U & Brouwer, MC 2022, 'The role of plasminogen activator inhibitor-2 in pneumococcal meningitis', Acta neuropathologica communications, vol. 10, no. 1, 155. https://doi.org/10.1186/s40478-022-01461-1

APA

Teske, N. C., Engelen-Lee, J-Y., Dyckhoff-Shen, S., Pfister, H-W., Klein, M., van de Beek, D., Kirschning, C. K., Koedel, U., & Brouwer, M. C. (2022). The role of plasminogen activator inhibitor-2 in pneumococcal meningitis. Acta neuropathologica communications, 10(1), [155]. https://doi.org/10.1186/s40478-022-01461-1

Vancouver

Teske NC, Engelen-Lee J-Y, Dyckhoff-Shen S, Pfister H-W, Klein M, van de Beek D et al. The role of plasminogen activator inhibitor-2 in pneumococcal meningitis. Acta neuropathologica communications. 2022 Dec 1;10(1):155. doi: 10.1186/s40478-022-01461-1

Author

Teske, Nina C. ; Engelen-Lee, Joo-Yeon ; Dyckhoff-Shen, Susanne et al. / The role of plasminogen activator inhibitor-2 in pneumococcal meningitis. In: Acta neuropathologica communications. 2022 ; Vol. 10, No. 1.

BibTeX

@article{a739dfd3447646db96485b7343d9516d,
title = "The role of plasminogen activator inhibitor-2 in pneumococcal meningitis",
abstract = "Pneumococcal meningitis is associated with dysregulation of the coagulation cascade. Previously, we detected upregulation of cerebral plasminogen activator inhibitor-2 (PAI-2) mRNA expression during pneumococcal meningitis. Diverse functions have been ascribed to PAI-2, but its role remains unclear. We analyzed the function of SERPINB2 (coding for PAI-2) in patients with bacterial meningitis, in a well-established pneumococcal meningitis mouse model, using Serpinb2 knockout mice, and in vitro in wt and PAI-2-deficient bone marrow-derived macrophages (BMDMs). We measured PAI-2 in cerebrospinal fluid of patients, and performed functional, histopathological, protein and mRNA expression analyses in vivo and in vitro. We found a substantial increase of PAI-2 concentration in CSF of patients with pneumococcal meningitis, and up-regulation and increased release of PAI-2 in mice. PAI-2 deficiency was associated with increased mortality in murine pneumococcal meningitis and cerebral hemorrhages. Serpinb2−/− mice exhibited increased C5a levels, but decreased IL-10 levels in the brain during pneumococcal infection. Our in vitro experiments confirmed increased expression and release of PAI-2 by wt BMDM and decreased IL-10 liberation by PAI-2-deficient BMDM upon pneumococcal challenge. Our data show that PAI-2 is elevated during in pneumococcal meningitis in humans and mice. PAI-2 deficiency causes an inflammatory imbalance, resulting in increased brain pathology and mortality.",
keywords = "Plasminogen activator inhibitor-2, Pneumococcal meningitis, SERPINB2",
author = "Teske, {Nina C.} and Joo-Yeon Engelen-Lee and Susanne Dyckhoff-Shen and Hans-Walter Pfister and Matthias Klein and {van de Beek}, Diederik and Kirschning, {Carsten K.} and Uwe Koedel and Brouwer, {Matthijs C.}",
note = "Funding Information: This study has been funded by grants from the European Society of Clinical Microbiology and Infectious Diseases (ESCMID Research Grant 2011 to MCB), European Federation of Neurological Sciences (EFNS Scientific Fellowship 2011 to MCB), Netherlands Organization for Health Research and Development (ZonMw; NWO-Veni grant 2012 [916.13.078] to MCB. The study was performed as collaborative project of the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections of the Brain (ESGIB). Funding Information: We thank Barbara Angele for technical support, and all Dutch physicians participating in the MeninGene study. MCB is supported by a grant from the Netherlands Organization for Health Research and Development (ZonMw; NWO-Vidi Grant 2017 [917.17.308]) and the European Research Council (ERC Consolidator Grant 2021 [101001237]). DvdB is supported by grants from the Netherlands Organization for Health Research and Development (ZonMw; ZonMw; NWO-Vici grant 2019 [918.196.27] to DvdB). UK is supported by grants from the German research Foundation (UK1974/9-1 und UK1974/10-1). Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
day = "1",
doi = "10.1186/s40478-022-01461-1",
language = "English",
volume = "10",
journal = "Acta neuropathologica communications",
issn = "2051-5960",
publisher = "BioMed Central",
number = "1",

}

RIS

TY - JOUR

T1 - The role of plasminogen activator inhibitor-2 in pneumococcal meningitis

AU - Teske, Nina C.

AU - Engelen-Lee, Joo-Yeon

AU - Dyckhoff-Shen, Susanne

AU - Pfister, Hans-Walter

AU - Klein, Matthias

AU - van de Beek, Diederik

AU - Kirschning, Carsten K.

AU - Koedel, Uwe

AU - Brouwer, Matthijs C.

N1 - Funding Information: This study has been funded by grants from the European Society of Clinical Microbiology and Infectious Diseases (ESCMID Research Grant 2011 to MCB), European Federation of Neurological Sciences (EFNS Scientific Fellowship 2011 to MCB), Netherlands Organization for Health Research and Development (ZonMw; NWO-Veni grant 2012 [916.13.078] to MCB. The study was performed as collaborative project of the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections of the Brain (ESGIB). Funding Information: We thank Barbara Angele for technical support, and all Dutch physicians participating in the MeninGene study. MCB is supported by a grant from the Netherlands Organization for Health Research and Development (ZonMw; NWO-Vidi Grant 2017 [917.17.308]) and the European Research Council (ERC Consolidator Grant 2021 [101001237]). DvdB is supported by grants from the Netherlands Organization for Health Research and Development (ZonMw; ZonMw; NWO-Vici grant 2019 [918.196.27] to DvdB). UK is supported by grants from the German research Foundation (UK1974/9-1 und UK1974/10-1). Publisher Copyright: © 2022, The Author(s).

PY - 2022/12/1

Y1 - 2022/12/1

N2 - Pneumococcal meningitis is associated with dysregulation of the coagulation cascade. Previously, we detected upregulation of cerebral plasminogen activator inhibitor-2 (PAI-2) mRNA expression during pneumococcal meningitis. Diverse functions have been ascribed to PAI-2, but its role remains unclear. We analyzed the function of SERPINB2 (coding for PAI-2) in patients with bacterial meningitis, in a well-established pneumococcal meningitis mouse model, using Serpinb2 knockout mice, and in vitro in wt and PAI-2-deficient bone marrow-derived macrophages (BMDMs). We measured PAI-2 in cerebrospinal fluid of patients, and performed functional, histopathological, protein and mRNA expression analyses in vivo and in vitro. We found a substantial increase of PAI-2 concentration in CSF of patients with pneumococcal meningitis, and up-regulation and increased release of PAI-2 in mice. PAI-2 deficiency was associated with increased mortality in murine pneumococcal meningitis and cerebral hemorrhages. Serpinb2−/− mice exhibited increased C5a levels, but decreased IL-10 levels in the brain during pneumococcal infection. Our in vitro experiments confirmed increased expression and release of PAI-2 by wt BMDM and decreased IL-10 liberation by PAI-2-deficient BMDM upon pneumococcal challenge. Our data show that PAI-2 is elevated during in pneumococcal meningitis in humans and mice. PAI-2 deficiency causes an inflammatory imbalance, resulting in increased brain pathology and mortality.

AB - Pneumococcal meningitis is associated with dysregulation of the coagulation cascade. Previously, we detected upregulation of cerebral plasminogen activator inhibitor-2 (PAI-2) mRNA expression during pneumococcal meningitis. Diverse functions have been ascribed to PAI-2, but its role remains unclear. We analyzed the function of SERPINB2 (coding for PAI-2) in patients with bacterial meningitis, in a well-established pneumococcal meningitis mouse model, using Serpinb2 knockout mice, and in vitro in wt and PAI-2-deficient bone marrow-derived macrophages (BMDMs). We measured PAI-2 in cerebrospinal fluid of patients, and performed functional, histopathological, protein and mRNA expression analyses in vivo and in vitro. We found a substantial increase of PAI-2 concentration in CSF of patients with pneumococcal meningitis, and up-regulation and increased release of PAI-2 in mice. PAI-2 deficiency was associated with increased mortality in murine pneumococcal meningitis and cerebral hemorrhages. Serpinb2−/− mice exhibited increased C5a levels, but decreased IL-10 levels in the brain during pneumococcal infection. Our in vitro experiments confirmed increased expression and release of PAI-2 by wt BMDM and decreased IL-10 liberation by PAI-2-deficient BMDM upon pneumococcal challenge. Our data show that PAI-2 is elevated during in pneumococcal meningitis in humans and mice. PAI-2 deficiency causes an inflammatory imbalance, resulting in increased brain pathology and mortality.

KW - Plasminogen activator inhibitor-2

KW - Pneumococcal meningitis

KW - SERPINB2

UR - http://www.scopus.com/inward/record.url?scp=85140905472&partnerID=8YFLogxK

U2 - 10.1186/s40478-022-01461-1

DO - 10.1186/s40478-022-01461-1

M3 - Article

C2 - 36309755

VL - 10

JO - Acta neuropathologica communications

JF - Acta neuropathologica communications

SN - 2051-5960

IS - 1

M1 - 155

ER -

ID: 26574334