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Identifying platelet-derived factors as amplifiers of B. burgdorferi-induced cytokine production
Previous studies have shown that monocytes can be ‘trained’ or tolerized by certain stimuli to respond stronger or weaker to a secondary stimulation. Rewiring of glucose metabolism was found to be important in inducing this phenotype. As we previously found that Borrelia burgdorferi (B. burgdorferi)...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9585555/ https://www.ncbi.nlm.nih.gov/pubmed/36001729 http://dx.doi.org/10.1093/cei/uxac073 |
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author | Kerstholt, Mariska van de Schoor, Freek R Oosting, Marije Moorlag, Simone J C F M Li, Yang Jaeger, Martin van der Heijden, Wouter A Tunjungputri, Rahajeng N dos Santos, Jéssica C Kischkel, Brenda Vrijmoeth, Hedwig D Baarsma, M E Kullberg, Bart-Jan Lupse, Mihaela Hovius, Joppe W van den Wijngaard, Cees C Netea, Mihai G de Mast, Quirijn Joosten, Leo A B |
author_facet | Kerstholt, Mariska van de Schoor, Freek R Oosting, Marije Moorlag, Simone J C F M Li, Yang Jaeger, Martin van der Heijden, Wouter A Tunjungputri, Rahajeng N dos Santos, Jéssica C Kischkel, Brenda Vrijmoeth, Hedwig D Baarsma, M E Kullberg, Bart-Jan Lupse, Mihaela Hovius, Joppe W van den Wijngaard, Cees C Netea, Mihai G de Mast, Quirijn Joosten, Leo A B |
author_sort | Kerstholt, Mariska |
collection | PubMed |
description | Previous studies have shown that monocytes can be ‘trained’ or tolerized by certain stimuli to respond stronger or weaker to a secondary stimulation. Rewiring of glucose metabolism was found to be important in inducing this phenotype. As we previously found that Borrelia burgdorferi (B. burgdorferi), the causative agent of Lyme borreliosis (LB), alters glucose metabolism in monocytes, we hypothesized that this may also induce long-term changes in innate immune responses. We found that exposure to B. burgdorferi decreased cytokine production in response to the TLR4-ligand lipopolysaccharide (LPS). In addition, B. burgdorferi exposure decreased baseline levels of glycolysis, as assessed by lactate production. Using GWAS analysis, we identified a gene, microfibril-associated protein 3-like (MFAP3L) as a factor influencing lactate production after B. burgdorferi exposure. Validation experiments proved that MFAP3L affects lactate- and cytokine production following B. burgdorferi stimulation. This is mediated by functions of MFAP3L, which includes activating ERK2 and through activation of platelet degranulation. Moreover, we showed that platelets and platelet-derived factors play important roles in B. burgdorferi-induced cytokine production. Certain platelet-derived factors, such chemokine C-X-C motif ligand 7 (CXCL7) and (C-C motif) ligand 5 (CCL5), were elevated in the circulation of LB patients in comparison to healthy individuals. |
format | Online Article Text |
id | pubmed-9585555 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-95855552022-10-24 Identifying platelet-derived factors as amplifiers of B. burgdorferi-induced cytokine production Kerstholt, Mariska van de Schoor, Freek R Oosting, Marije Moorlag, Simone J C F M Li, Yang Jaeger, Martin van der Heijden, Wouter A Tunjungputri, Rahajeng N dos Santos, Jéssica C Kischkel, Brenda Vrijmoeth, Hedwig D Baarsma, M E Kullberg, Bart-Jan Lupse, Mihaela Hovius, Joppe W van den Wijngaard, Cees C Netea, Mihai G de Mast, Quirijn Joosten, Leo A B Clin Exp Immunol Research Articles Previous studies have shown that monocytes can be ‘trained’ or tolerized by certain stimuli to respond stronger or weaker to a secondary stimulation. Rewiring of glucose metabolism was found to be important in inducing this phenotype. As we previously found that Borrelia burgdorferi (B. burgdorferi), the causative agent of Lyme borreliosis (LB), alters glucose metabolism in monocytes, we hypothesized that this may also induce long-term changes in innate immune responses. We found that exposure to B. burgdorferi decreased cytokine production in response to the TLR4-ligand lipopolysaccharide (LPS). In addition, B. burgdorferi exposure decreased baseline levels of glycolysis, as assessed by lactate production. Using GWAS analysis, we identified a gene, microfibril-associated protein 3-like (MFAP3L) as a factor influencing lactate production after B. burgdorferi exposure. Validation experiments proved that MFAP3L affects lactate- and cytokine production following B. burgdorferi stimulation. This is mediated by functions of MFAP3L, which includes activating ERK2 and through activation of platelet degranulation. Moreover, we showed that platelets and platelet-derived factors play important roles in B. burgdorferi-induced cytokine production. Certain platelet-derived factors, such chemokine C-X-C motif ligand 7 (CXCL7) and (C-C motif) ligand 5 (CCL5), were elevated in the circulation of LB patients in comparison to healthy individuals. Oxford University Press 2022-08-24 /pmc/articles/PMC9585555/ /pubmed/36001729 http://dx.doi.org/10.1093/cei/uxac073 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Immunology. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Kerstholt, Mariska van de Schoor, Freek R Oosting, Marije Moorlag, Simone J C F M Li, Yang Jaeger, Martin van der Heijden, Wouter A Tunjungputri, Rahajeng N dos Santos, Jéssica C Kischkel, Brenda Vrijmoeth, Hedwig D Baarsma, M E Kullberg, Bart-Jan Lupse, Mihaela Hovius, Joppe W van den Wijngaard, Cees C Netea, Mihai G de Mast, Quirijn Joosten, Leo A B Identifying platelet-derived factors as amplifiers of B. burgdorferi-induced cytokine production |
title | Identifying platelet-derived factors as amplifiers of B. burgdorferi-induced cytokine production |
title_full | Identifying platelet-derived factors as amplifiers of B. burgdorferi-induced cytokine production |
title_fullStr | Identifying platelet-derived factors as amplifiers of B. burgdorferi-induced cytokine production |
title_full_unstemmed | Identifying platelet-derived factors as amplifiers of B. burgdorferi-induced cytokine production |
title_short | Identifying platelet-derived factors as amplifiers of B. burgdorferi-induced cytokine production |
title_sort | identifying platelet-derived factors as amplifiers of b. burgdorferi-induced cytokine production |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9585555/ https://www.ncbi.nlm.nih.gov/pubmed/36001729 http://dx.doi.org/10.1093/cei/uxac073 |
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