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Citations to this article

Complement component 5 contributes to poor disease outcome in humans and mice with pneumococcal meningitis
Bianca Woehrl, … , Uwe Koedel, Diederik van de Beek
Bianca Woehrl, … , Uwe Koedel, Diederik van de Beek
Published September 19, 2011
Citation Information: J Clin Invest. 2011;121(10):3943-3953. https://doi.org/10.1172/JCI57522.
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Research Article Immunology Article has an altmetric score of 7

Complement component 5 contributes to poor disease outcome in humans and mice with pneumococcal meningitis

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Abstract

Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the proinflammatory response in the subarachnoid space. The complement system, which mediates key inflammatory processes, has been implicated as a modulator of pneumococcal meningitis disease severity in animal studies. Additionally, SNPs in genes encoding complement pathway proteins have been linked to susceptibility to pneumococcal infection, although no associations with disease severity or outcome have been established. Here, we have performed a robust prospective nationwide genetic association study in patients with bacterial meningitis and found that a common nonsynonymous complement component 5 (C5) SNP (rs17611) is associated with unfavorable disease outcome. C5 fragment levels in cerebrospinal fluid (CSF) of patients with bacterial meningitis correlated with several clinical indicators of poor prognosis. Consistent with these human data, C5a receptor–deficient mice with pneumococcal meningitis had lower CSF wbc counts and decreased brain damage compared with WT mice. Adjuvant treatment with C5-specific monoclonal antibodies prevented death in all mice with pneumococcal meningitis. Thus, our results suggest C5-specific monoclonal antibodies could be a promising new antiinflammatory adjuvant therapy for pneumococcal meningitis.

Authors

Bianca Woehrl, Matthijs C. Brouwer, Carmen Murr, Sebastiaan G.B. Heckenberg, Frank Baas, Hans W. Pfister, Aeilko H. Zwinderman, B. Paul Morgan, Scott R. Barnum, Arie van der Ende, Uwe Koedel, Diederik van de Beek

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Total citations by year

Year: 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2009 Total
Citations: 4 3 3 4 4 7 2 5 6 5 4 4 3 1 55
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Citations to this article (55)

Title and authors Publication Year
Combining antibiotic therapy with TLR2 and TLR13 blockade averts brain pathology in murine pneumococcal meningitis
Susanne Dyckhoff-Shen, Ilias Masouris, Sven Hammerschmidt, Barbara Angele, Veena Marathe, jan Buer, Stefanie Völk, Hans-Walter Pfister, Matthias Klein, Uwe Koedel, Carsten J. Kirschning
JCI Insight 2024
Adjunctive treatments for pneumococcal meningitis: a systematic review of experimental animal models.
Koning R, van Roon MA, Brouwer MC, van de Beek D
2024
Advances in the pathogenesis and treatment of pneumococcal meningitis
Xu Y, Wang J, Qin X, Liu J
Virulence 2024
Complement System and Adhesion Molecule Skirmishes in Fabry Disease: Insights into Pathogenesis and Disease Mechanisms
Magnusen AF, Pandey MK
International Journal of Molecular Sciences 2024
Pericytes are protective in experimental pneumococcal meningitis through regulating leukocyte infiltration and blood-brain barrier function
Nina Teske, Susanne Dyckhoff-Shen, Paul Beckenbauer, Jan Bewersdorf, Joo-Yeon Engelen-Lee, Sven Hammerschmidt, Roland Kälin, Hans-Walter Pfister, Matthijs Brouwer, Matthias Klein, Rainer Glass, Diederik Beek, Uwe Koedel
Journal of Neuroinflammation 2023
The Relationship between Complement Components C1R and C5 Gene Polymorphism and the Values of Blood Indices in Suckling Piglets
Szymańska H, Dzika E, Zabolewicz TJ, Życzko K
Genes & development 2023
Blockade of C5a receptor unleashes tumor-associated macrophage antitumor response and enhances CXCL9-dependent CD8+ T cell activity
Luan X, Lei T, Fang J, Liu X, Fu H, Li Y, Chu W, Jiang P, Tong C, Qi H, Fu Y
Molecular Therapy 2023
Streptococcus pneumoniae interactions with the complement system
Gil E, Noursadeghi M, Brown JS
Frontiers in Cellular and Infection Microbiology 2022
The role of plasminogen activator inhibitor-2 in pneumococcal meningitis.
Teske NC, Engelen-Lee JY, Dyckhoff-Shen S, Pfister HW, Klein M, van de Beek D, Kirschning CK, Koedel U, Brouwer MC
Acta Neuropathologica Communications 2022
Low serum complement level is associated with higher mortality in tuberculous meningitis: a retrospective cohort study
Im H, Kim T, Na S, Song IU, Kim SH, Oh YS, Oh J, Kim W
2022
The search for novel treatment strategies for Streptococcus pneumoniae infections
F Cools, P Delputte, P Cos
FEMS Microbiology Reviews 2021
The Influence of an Elastase-Sensitive Complement C5 Variant on Lupus Nephritis and Its Flare
CR Toy, H Song, HN Nagaraja, J Scott, J Greco, X Zhang, CY Yu, JA Tumlin, BH Rovin, LA Hebert, DJ Birmingham
Kidney International Reports 2021
Interaction Between the Complement System and Infectious Agents – A Potential Mechanistic Link to Neurodegeneration and Dementia
N Shinjyo, W Kagaya, M Pekna
Frontiers in cellular neuroscience 2021
Investigation of Association of Complement 5 Genetic Polymorphisms with Sepsis and Sepsis-Induced Inflammatory Responses
K Chen, Y Lin, Y Liu, S Liao, R Yang, J Huang, M Xu, J He
Journal of inflammation research 2021
Cronobacter sakazakii Infection in Early Postnatal Rats Impaired Contextual-Associated Learning: a Putative Role of C5a-Mediated NF-κβ and ASK1 Pathways
P Vinay, C Karen, K Balamurugan, KE Rajan
Journal of Molecular Neuroscience 2020
Soluble Membrane Attack Complex: Biochemistry and Immunobiology
SR Barnum, D Bubeck, TN Schein
Frontiers in immunology 2020
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V Giudice, P Pagliano, A Vatrella, A Masullo, S Poto, BM Polverino, R Gammaldi, A Maglio, C Sellitto, C Vitale, B Serio, B Cuffa, A Borrelli, C Vecchione, A Filippelli, C Selleri
Frontiers in pharmacology 2020
Characterizing the original anti‐C5 function‐blocking antibody, BB5.1, for species specificity, mode of action and interactions with C5
WM Zelek, GE Menzies, A Brancale, B Stockinger, BP Morgan
Immunology 2020
Complement C5 Contributes to Brain Injury After Subarachnoid Hemorrhage
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Translational Stroke Research 2019
Common Genetic Variants in the Complement System and their Potential Link with Disease Susceptibility and Outcome of Invasive Bacterial Infection
B van den Broek, M van der Flier, R de Groot, MI de Jonge, JD Langereis
Journal of Innate Immunity 2019
Combining Ceftriaxone with Doxycycline and Daptomycin Reduces Mortality, Neuroinflammation, Brain Damage, and Hearing Loss in Infant Rat Pneumococcal Meningitis
L Muri, M Perny, J Zemp, D Grandgirard, SL Leib
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ES Kasanmoentalib, MV Serón, JY Engelen-Lee, MW Tanck, RB Pouw, G van Mierlo, D Wouters, MC Pickering, A van der Ende, TW Kuijpers, MC Brouwer, D van de Beek
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J Fritscher, D Amberger, S Dyckhoff, JP Bewersdorf, I Masouris, S Voelk, S Hammerschmidt, HM Schmetzer, M Klein, HW Pfister, U Koedel
Frontiers in immunology 2018
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Role of purinergic signaling in experimental pneumococcal meningitis
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Inhibition of DAMP signaling as an effective adjunctive treatment strategy in pneumococcal meningitis
I Masouris, M Klein, S Dyckhoff, B Angele, HW Pfister, U Koedel
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Alternative Pathway Inhibition by Exogenous Factor H Fails to Attenuate Inflammation and Vascular Leakage in Experimental Pneumococcal Sepsis in Mice
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Complement component C3a plays a critical role in endothelial activation and leukocyte recruitment into the brain
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