Merel M Koopmans1, Matthijs C Brouwer1, Madelijn Geldhoff1, Mercedes Valls Seron1, Judith Houben1, Arie van der Ende2, Diederik van de Beek1. 1. Department of Neurology, Academic Medical Center, University of Amsterdam, Center for Infection and Immunity Amsterdam (CINIMA), Amsterdam, The Netherlands. 2. Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Center for Infection and Immunity Amsterdam (CINIMA), Amsterdam, The Netherlands ; The Netherlands Reference Laboratory for Bacterial Meningitis, Amsterdam, The Netherlands.
Abstract
BACKGROUND: Listeria monocytogenes meningitis is the third most common cause of bacterial meningitis and is associated with high rates of mortality and unfavorable outcome. METHODS: We analyzed 101 cytokines, chemokines and complement factors in CSF of adult patients with Listeria meningitis included in a prospective cohort study and compared these biomarkers between Listeria meningitis patients and negative controls, and between Listeria meningitis patients with a favorable and an unfavorable outcome. RESULTS: CSF was available from 26 of 62 (42%) Listeria meningitis patients and 19 negative controls. Fifteen (58%) Listeria meningitis patients had an unfavorable outcome. In Listeria meningitis CSF levels of 51 biomarkers were significantly elevated compared to negative controls after Bonferroni correction. The 11 most significantly elevated (P < .01) biomarkers of unfavorable outcome in Listeria meningitis were markers of T-cell activation (sIL-2Rα, sCD40L and IL-1), interferon-related (IFN-α2, IL-18, CX3CL1, CCL20), markers of complement activation (C3a), and endothelial growth factor related (VEGF, CXCL7). CONCLUSIONS: Our data suggest that T-cell activation, complement activation, interferon- and endothelial growth factor production are important in the immune response to Listeria meningitis, and thereby influence outcome. GENERAL SIGNIFICANCE: Our study provides target pathways for further studies in the pathophysiology of Listeria meningitis.
BACKGROUND:Listeria monocytogenesmeningitis is the third most common cause of bacterial meningitis and is associated with high rates of mortality and unfavorable outcome. METHODS: We analyzed 101 cytokines, chemokines and complement factors in CSF of adult patients with Listeria meningitis included in a prospective cohort study and compared these biomarkers between Listeria meningitispatients and negative controls, and between Listeria meningitispatients with a favorable and an unfavorable outcome. RESULTS: CSF was available from 26 of 62 (42%) Listeria meningitispatients and 19 negative controls. Fifteen (58%) Listeria meningitispatients had an unfavorable outcome. In Listeria meningitis CSF levels of 51 biomarkers were significantly elevated compared to negative controls after Bonferroni correction. The 11 most significantly elevated (P < .01) biomarkers of unfavorable outcome in Listeria meningitis were markers of T-cell activation (sIL-2Rα, sCD40L and IL-1), interferon-related (IFN-α2, IL-18, CX3CL1, CCL20), markers of complement activation (C3a), and endothelial growth factor related (VEGF, CXCL7). CONCLUSIONS: Our data suggest that T-cell activation, complement activation, interferon- and endothelial growth factor production are important in the immune response to Listeria meningitis, and thereby influence outcome. GENERAL SIGNIFICANCE: Our study provides target pathways for further studies in the pathophysiology of Listeria meningitis.
Authors: Admar Verschoor; Michael Neuenhahn; Alexander A Navarini; Patricia Graef; Ann Plaumann; Amelie Seidlmeier; Bernhard Nieswandt; Steffen Massberg; Rolf M Zinkernagel; Hans Hengartner; Dirk H Busch Journal: Nat Immunol Date: 2011-10-30 Impact factor: 25.606
Authors: Merel M Koopmans; Matthijs C Brouwer; Merijn W Bijlsma; Sandra Bovenkerk; Wendy Keijzers; Arie van der Ende; Diederik van de Beek Journal: Clin Infect Dis Date: 2013-04-16 Impact factor: 9.079
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 Journal: J Clin Invest Date: 2011-09-19 Impact factor: 14.808
Authors: Ryan M O'Connell; Supriya K Saha; Sagar A Vaidya; Kevin W Bruhn; Gustavo A Miranda; Brian Zarnegar; Andrea K Perry; Bidong O Nguyen; Timothy F Lane; Tadatsugu Taniguchi; Jeff F Miller; Genhong Cheng Journal: J Exp Med Date: 2004-08-09 Impact factor: 14.307
Authors: Bart Ferwerda; Mercedes Valls Serón; Aldo Jongejan; Aeilko H Zwinderman; Madelijn Geldhoff; Arie van der Ende; Frank Baas; Matthijs C Brouwer; Diederik van de Beek Journal: EBioMedicine Date: 2016-07-12 Impact factor: 8.143
Authors: Florian R Zbinden; Megan De Ste Croix; Denis Grandgirard; Richard D Haigh; Irene Vacca; Roxana Zamudio; Emily C A Goodall; Roger Stephan; Marco R Oggioni; Stephen L Leib Journal: Front Cell Infect Microbiol Date: 2020-10-30 Impact factor: 5.293