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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.<\/jats:p>","DOI":"10.1093\/cei\/uxac073","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T18:17:13Z","timestamp":1661365033000},"page":"53-67","source":"Crossref","is-referenced-by-count":5,"title":["Identifying platelet-derived factors as amplifiers of<i>B. burgdorferi<\/i>-induced cytokine production"],"prefix":"10.1093","volume":"210","author":[{"given":"Mariska","family":"Kerstholt","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Radboudumc Center for Infectious diseases (RCI), Radboud University Medical Center , Nijmegen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2358-9335","authenticated-orcid":false,"given":"Freek R","family":"van de 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Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahajeng N","family":"Tunjungputri","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboudumc Center for Infectious diseases (RCI), Radboud University Medical Center , Nijmegen , The Netherlands"},{"name":"Center for Tropical and Infectious Diseases (CENTRID), Faculty of Medicine Diponegoro University, Dr. Kariadi Hospital , Semarang , Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9ssica C","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboudumc Center for Infectious diseases (RCI), Radboud University Medical Center , Nijmegen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Kischkel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Institute of Molecular Life Sciences (RIMLS), Radboud 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