Cytokine response in cerebrospinal fluid of meningitis patients and outcome associated with pneumococcal serotype

Müller, Annelies; Schramm, Diana B; Kleynhans, Jackie; de Gouveia, Linda; Meiring, Susan; Ramette, Alban; von Gottberg, Anne; Hathaway, Lucy Jane (2021). Cytokine response in cerebrospinal fluid of meningitis patients and outcome associated with pneumococcal serotype. Scientific reports, 11(1), p. 19920. Springer Nature 10.1038/s41598-021-99190-3

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Streptococcus pneumoniae causes life-threatening meningitis. Its capsular polysaccharide determines the serotype and influences disease severity but the mechanism is largely unknown. Due to evidence of elevated cytokines levels in the meningeal inflammatory response, we measured 41 cytokines/chemokines and growth factors in cerebrospinal fluid (CSF) samples from 57 South African meningitis patients (collected in the period 2018-2019), with confirmed S. pneumoniae serotypes, using a multiplexed bead-based immunoassay. Based on multivariable Bayesian regression, using serotype 10A as a reference and after adjusting for HIV and age, we found IL-6 concentrations significantly lower in patients infected with serotypes 6D (undetectable) and 23A (1601 pg/ml), IL-8 concentrations significantly higher in those infected with 22A (40,459 pg/ml), 7F (32,400 pg/ml) and 15B/C (6845 pg/ml), and TNFα concentration significantly higher in those infected with serotype 18A (33,097 pg/ml). Although a relatively small number of clinical samples were available for this study and 28% of samples could not be assigned to a definitive serotype, our data suggests 15B/C worthy of monitoring during surveillance as it is associated with in-hospital case fatality and not included in the 13-valent polysaccharide conjugate vaccine, PCV13. Our data provides average CSF concentrations of a range of cytokines and growth factors for 18 different serotypes (14, 19F, 3, 6A, 7F, 19A, 8, 9N, 10A, 12F, 15B/C, 22F, 16F, 23A, 31, 18A, 6D, 22A) to serve as a basis for future studies investigating host-pathogen interaction during pneumococcal meningitis. We note that differences in induction of IL-8 between serotypes may be particularly worthy of future study.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Müller, Annelies Kathrin; Ramette, Alban Nicolas and Hathaway, Lucy Jane

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2045-2322

Publisher:

Springer Nature

Funders:

[4] Swiss National Science Foundation ; [UNSPECIFIED] National Research Foundation of South Africa

Language:

English

Submitter:

Lucy Jane Hathaway

Date Deposited:

08 Nov 2021 09:27

Last Modified:

14 Nov 2021 01:45

Publisher DOI:

10.1038/s41598-021-99190-3

PubMed ID:

34620928

BORIS DOI:

10.48350/159979

URI:

https://boris.unibe.ch/id/eprint/159979

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