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Whole-blood incubation with the Neisseria meningitidis lpxL1 mutant induces less pro-inflammatory cytokines than the wild type, and IL-10 reduces the MyD88-dependent cytokines
Levels of bacterial LPS, pro-inflammatory cytokines and IL-10 are related to the severity of meningococcal septicaemia. Patients infected with a Neisseria meninigitidis lpxL1 mutant (Nm-mutant) with penta-acylated lipid A present with a milder meningococcal disease than those infected with hexa-acyl...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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SAGE Publications
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830899/ https://www.ncbi.nlm.nih.gov/pubmed/29313733 http://dx.doi.org/10.1177/1753425917749299 |
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author | Aass, Hans Christian D Hellum, Marit Trøseid, Anne-Marie Siebke Brandtzaeg, Petter Berg, Jens Petter Øvstebø, Reidun Henriksson, Carola Elisabeth |
author_facet | Aass, Hans Christian D Hellum, Marit Trøseid, Anne-Marie Siebke Brandtzaeg, Petter Berg, Jens Petter Øvstebø, Reidun Henriksson, Carola Elisabeth |
author_sort | Aass, Hans Christian D |
collection | PubMed |
description | Levels of bacterial LPS, pro-inflammatory cytokines and IL-10 are related to the severity of meningococcal septicaemia. Patients infected with a Neisseria meninigitidis lpxL1 mutant (Nm-mutant) with penta-acylated lipid A present with a milder meningococcal disease than those infected with hexa-acylated Nm wild type (Nm-wt). The aim was to compare the pro-inflammatory responses after ex vivo incubation with the heat-inactivated Nm-wt or the Nm-mutant in citrated whole blood, and the modulating effects of IL-10. Concomitantly, we measured intracellular IL-6, IL-8 and TNF-α to elucidate which cell types were responsible for the pro-inflammatory responses. Incubation with Nm-wt (10(6)/ml;10(7)/ml;10(8)/ml) resulted in a dose-dependent increase of the MyD88-dependent pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α), which were mainly derived from monocytes. In comparison, only 10(8)/ml of the Nm-mutant significantly increased the concentration of these cytokines. The MyD88-independent cytokines (IP-10, RANTES) were evidently increased after incubation with the Nm-wt but were unaffected by the Nm-mutant. Co-incubation with IL-10 significantly reduced the concentrations of the MyD88-dependent cytokines induced by both the Nm-wt and the Nm-mutant, whereas the MyD88-independent cytokines were almost unaffected. In summary, the Nm-mutant is a weaker inducer of the MyD88-dependent/independent cytokines than the Nm-wt in whole blood, and IL-10 attenuates the Nm-stimulated increase in MyD88-dependent pro-inflammatory cytokines. |
format | Online Article Text |
id | pubmed-6830899 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-68308992019-11-20 Whole-blood incubation with the Neisseria meningitidis lpxL1 mutant induces less pro-inflammatory cytokines than the wild type, and IL-10 reduces the MyD88-dependent cytokines Aass, Hans Christian D Hellum, Marit Trøseid, Anne-Marie Siebke Brandtzaeg, Petter Berg, Jens Petter Øvstebø, Reidun Henriksson, Carola Elisabeth Innate Immun Original Articles Levels of bacterial LPS, pro-inflammatory cytokines and IL-10 are related to the severity of meningococcal septicaemia. Patients infected with a Neisseria meninigitidis lpxL1 mutant (Nm-mutant) with penta-acylated lipid A present with a milder meningococcal disease than those infected with hexa-acylated Nm wild type (Nm-wt). The aim was to compare the pro-inflammatory responses after ex vivo incubation with the heat-inactivated Nm-wt or the Nm-mutant in citrated whole blood, and the modulating effects of IL-10. Concomitantly, we measured intracellular IL-6, IL-8 and TNF-α to elucidate which cell types were responsible for the pro-inflammatory responses. Incubation with Nm-wt (10(6)/ml;10(7)/ml;10(8)/ml) resulted in a dose-dependent increase of the MyD88-dependent pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α), which were mainly derived from monocytes. In comparison, only 10(8)/ml of the Nm-mutant significantly increased the concentration of these cytokines. The MyD88-independent cytokines (IP-10, RANTES) were evidently increased after incubation with the Nm-wt but were unaffected by the Nm-mutant. Co-incubation with IL-10 significantly reduced the concentrations of the MyD88-dependent cytokines induced by both the Nm-wt and the Nm-mutant, whereas the MyD88-independent cytokines were almost unaffected. In summary, the Nm-mutant is a weaker inducer of the MyD88-dependent/independent cytokines than the Nm-wt in whole blood, and IL-10 attenuates the Nm-stimulated increase in MyD88-dependent pro-inflammatory cytokines. SAGE Publications 2018-01-09 2018-02 /pmc/articles/PMC6830899/ /pubmed/29313733 http://dx.doi.org/10.1177/1753425917749299 Text en © The Author(s) 2018 http://creativecommons.org/licenses/by-nc/4.0/ Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Articles Aass, Hans Christian D Hellum, Marit Trøseid, Anne-Marie Siebke Brandtzaeg, Petter Berg, Jens Petter Øvstebø, Reidun Henriksson, Carola Elisabeth Whole-blood incubation with the Neisseria meningitidis lpxL1 mutant induces less pro-inflammatory cytokines than the wild type, and IL-10 reduces the MyD88-dependent cytokines |
title | Whole-blood incubation with the Neisseria meningitidis
lpxL1 mutant induces less pro-inflammatory cytokines than the wild
type, and IL-10 reduces the MyD88-dependent cytokines |
title_full | Whole-blood incubation with the Neisseria meningitidis
lpxL1 mutant induces less pro-inflammatory cytokines than the wild
type, and IL-10 reduces the MyD88-dependent cytokines |
title_fullStr | Whole-blood incubation with the Neisseria meningitidis
lpxL1 mutant induces less pro-inflammatory cytokines than the wild
type, and IL-10 reduces the MyD88-dependent cytokines |
title_full_unstemmed | Whole-blood incubation with the Neisseria meningitidis
lpxL1 mutant induces less pro-inflammatory cytokines than the wild
type, and IL-10 reduces the MyD88-dependent cytokines |
title_short | Whole-blood incubation with the Neisseria meningitidis
lpxL1 mutant induces less pro-inflammatory cytokines than the wild
type, and IL-10 reduces the MyD88-dependent cytokines |
title_sort | whole-blood incubation with the neisseria meningitidis
lpxl1 mutant induces less pro-inflammatory cytokines than the wild
type, and il-10 reduces the myd88-dependent cytokines |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830899/ https://www.ncbi.nlm.nih.gov/pubmed/29313733 http://dx.doi.org/10.1177/1753425917749299 |
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