Neisseria meningitidis-Induced Caspase-1 Activation in Human Innate Immune Cells Is LOS-Dependent
Meningococcal disease such as sepsis and meningitidis is hallmarked by an excessive inflammatory response. The causative agent, Neisseria meningitidis, expresses the endotoxin lipooligosaccharide (LOS) that is responsible for activation of immune cells and the release of proinflammatory cytokines. O...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-01-01
|
| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2019/6193186 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849690881416757248 |
|---|---|
| author | Berhane Asfaw Idosa Anne Kelly Susanne Jacobsson Isak Demirel Hans Fredlund Eva Särndahl Alexander Persson |
| author_facet | Berhane Asfaw Idosa Anne Kelly Susanne Jacobsson Isak Demirel Hans Fredlund Eva Särndahl Alexander Persson |
| author_sort | Berhane Asfaw Idosa |
| collection | DOAJ |
| description | Meningococcal disease such as sepsis and meningitidis is hallmarked by an excessive inflammatory response. The causative agent, Neisseria meningitidis, expresses the endotoxin lipooligosaccharide (LOS) that is responsible for activation of immune cells and the release of proinflammatory cytokines. One of the most potent proinflammatory cytokines, interleukin-1β (IL-1β), is activated following caspase-1 activity in the intracellular multiprotein complex called inflammasome. Inflammasomes are activated by a number of microbial factors as well as danger molecules by a two-step mechanism—priming and licensing of inflammasome activation—but there are no data available regarding a role for inflammasome activation in meningococcal disease. The aim of this study was to investigate if N. meningitidis activates the inflammasome and, if so, the role of bacterial LOS in this activation. Cells were subjected to N. meningitidis, both wild-type (FAM20) and its LOS-deficient mutant (lpxA), and priming as well as licensing of inflammasome activation was investigated. The wild-type LOS-expressing parental FAM20 serogroup C N. meningitidis (FAM20) strain significantly enhanced the caspase-1 activity in human neutrophils and monocytes, whereas lpxA was unable to induce caspase-1 activity as well as to induce IL-1β release. While the lpxA mutant induced a priming response, measured as increased expression of NLRP3 and IL1B, the LOS-expressing FAM20 further increased this priming. We conclude that although non-LOS components of N. meningitidis contribute to the priming of the inflammasome activity, LOS per se is to be considered as the central component of N. meningitidis virulence, responsible for both priming and licensing of inflammasome activation. |
| format | Article |
| id | doaj-art-ed5c1b26b21c4cb6a82aae686405bf9d |
| institution | DOAJ |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-ed5c1b26b21c4cb6a82aae686405bf9d2025-08-20T03:21:11ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/61931866193186Neisseria meningitidis-Induced Caspase-1 Activation in Human Innate Immune Cells Is LOS-DependentBerhane Asfaw Idosa0Anne Kelly1Susanne Jacobsson2Isak Demirel3Hans Fredlund4Eva Särndahl5Alexander Persson6iRiSC-Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, SwedeniRiSC-Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, SwedeniRiSC-Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, SwedeniRiSC-Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, SwedeniRiSC-Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, SwedeniRiSC-Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, SwedeniRiSC-Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, SwedenMeningococcal disease such as sepsis and meningitidis is hallmarked by an excessive inflammatory response. The causative agent, Neisseria meningitidis, expresses the endotoxin lipooligosaccharide (LOS) that is responsible for activation of immune cells and the release of proinflammatory cytokines. One of the most potent proinflammatory cytokines, interleukin-1β (IL-1β), is activated following caspase-1 activity in the intracellular multiprotein complex called inflammasome. Inflammasomes are activated by a number of microbial factors as well as danger molecules by a two-step mechanism—priming and licensing of inflammasome activation—but there are no data available regarding a role for inflammasome activation in meningococcal disease. The aim of this study was to investigate if N. meningitidis activates the inflammasome and, if so, the role of bacterial LOS in this activation. Cells were subjected to N. meningitidis, both wild-type (FAM20) and its LOS-deficient mutant (lpxA), and priming as well as licensing of inflammasome activation was investigated. The wild-type LOS-expressing parental FAM20 serogroup C N. meningitidis (FAM20) strain significantly enhanced the caspase-1 activity in human neutrophils and monocytes, whereas lpxA was unable to induce caspase-1 activity as well as to induce IL-1β release. While the lpxA mutant induced a priming response, measured as increased expression of NLRP3 and IL1B, the LOS-expressing FAM20 further increased this priming. We conclude that although non-LOS components of N. meningitidis contribute to the priming of the inflammasome activity, LOS per se is to be considered as the central component of N. meningitidis virulence, responsible for both priming and licensing of inflammasome activation.http://dx.doi.org/10.1155/2019/6193186 |
| spellingShingle | Berhane Asfaw Idosa Anne Kelly Susanne Jacobsson Isak Demirel Hans Fredlund Eva Särndahl Alexander Persson Neisseria meningitidis-Induced Caspase-1 Activation in Human Innate Immune Cells Is LOS-Dependent Journal of Immunology Research |
| title | Neisseria meningitidis-Induced Caspase-1 Activation in Human Innate Immune Cells Is LOS-Dependent |
| title_full | Neisseria meningitidis-Induced Caspase-1 Activation in Human Innate Immune Cells Is LOS-Dependent |
| title_fullStr | Neisseria meningitidis-Induced Caspase-1 Activation in Human Innate Immune Cells Is LOS-Dependent |
| title_full_unstemmed | Neisseria meningitidis-Induced Caspase-1 Activation in Human Innate Immune Cells Is LOS-Dependent |
| title_short | Neisseria meningitidis-Induced Caspase-1 Activation in Human Innate Immune Cells Is LOS-Dependent |
| title_sort | neisseria meningitidis induced caspase 1 activation in human innate immune cells is los dependent |
| url | http://dx.doi.org/10.1155/2019/6193186 |
| work_keys_str_mv | AT berhaneasfawidosa neisseriameningitidisinducedcaspase1activationinhumaninnateimmunecellsislosdependent AT annekelly neisseriameningitidisinducedcaspase1activationinhumaninnateimmunecellsislosdependent AT susannejacobsson neisseriameningitidisinducedcaspase1activationinhumaninnateimmunecellsislosdependent AT isakdemirel neisseriameningitidisinducedcaspase1activationinhumaninnateimmunecellsislosdependent AT hansfredlund neisseriameningitidisinducedcaspase1activationinhumaninnateimmunecellsislosdependent AT evasarndahl neisseriameningitidisinducedcaspase1activationinhumaninnateimmunecellsislosdependent AT alexanderpersson neisseriameningitidisinducedcaspase1activationinhumaninnateimmunecellsislosdependent |