{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T07:27:16Z","timestamp":1782631636163,"version":"3.54.5"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"10","license":[{"start":{"date-parts":[[2018,8,14]],"date-time":"2018-08-14T00:00:00Z","timestamp":1534204800000},"content-version":"vor","delay-in-days":181,"URL":"http:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2018,3,6]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Inflammation plays a crucial role in the pathogenesis of Lyme disease, caused by the spirochete\n                    <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                    . Intracellular metabolism is increasingly being recognized as a major determinant of inflammation. In this study, we investigated how\n                    <jats:italic>B. burgdorferi<\/jats:italic>\n                    affects host cell metabolism by analyzing the intracellular metabolome in vitro, as well as the circulating metabolome in patients with early-onset Lyme disease. We identify glutathione metabolism as the most important target of\n                    <jats:italic>B. burgdorferi<\/jats:italic>\n                    infection and discover that this pathway is essential for cytokine production, likely through glutathionylation. These findings not only provide more insight into the pathogenesis of Lyme disease but also underline how host\u2013pathogen interactions in metabolism can play crucial roles in host defense against pathogens.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1720833115","type":"journal-article","created":{"date-parts":[[2018,2,14]],"date-time":"2018-02-14T15:35:44Z","timestamp":1518622544000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":39,"title":["Role of glutathione metabolism in host defense against\n                    <i>Borrelia burgdorferi<\/i>\n                    infection"],"prefix":"10.1073","volume":"115","author":[{"given":"Mariska","family":"Kerstholt","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands;"},{"name":"Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hedwig","family":"Vrijmoeth","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands;"},{"name":"Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekta","family":"Lachmandas","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands;"},{"name":"Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marije","family":"Oosting","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands;"},{"name":"Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"Lupse","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, University of Medicine and Pharmacy \u201cIuliu Hatieganu,\u201d 400349 Cluj-Napoca, Romania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirela","family":"Flonta","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, University of Medicine and Pharmacy \u201cIuliu Hatieganu,\u201d 400349 Cluj-Napoca, Romania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A.","family":"Dinarello","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands;"},{"name":"Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands;"},{"name":"Department of Medicine, University of Colorado Denver, Aurora, CO 80045;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai G.","family":"Netea","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands;"},{"name":"Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands;"},{"name":"Human Genomics Laboratory, Craiova University of Medicine and Pharmacy, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo A. 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Curr Opin Rheumatol 14, 383\u2013387 (2002).","journal-title":"Curr Opin Rheumatol"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"25S","DOI":"10.1016\/S0002-9343(99)80041-2","article-title":"Early disseminated Lyme disease: Cardiac manifestations","volume":"98","author":"Sigal LH","year":"1995","unstructured":"LH Sigal, Early disseminated Lyme disease: Cardiac manifestations. Am J Med 98, 25S\u201328S, discussion 28S\u201329S (1995).","journal-title":"Am J Med"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/S1474-4422(07)70128-X","article-title":"Lyme neuroborreliosis: Infection, immunity, and inflammation","volume":"6","author":"Pachner AR","year":"2007","unstructured":"AR Pachner, I Steiner, Lyme neuroborreliosis: Infection, immunity, and inflammation. 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Mol Biosyst 12, 2471\u20132480 (2016).","journal-title":"Mol Biosyst"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"12157","DOI":"10.1073\/pnas.1401712111","article-title":"Linkage of inflammation and oxidative stress via release of glutathionylated peroxiredoxin-2, which acts as a danger signal","volume":"111","author":"Salzano S","year":"2014","unstructured":"S Salzano, , Linkage of inflammation and oxidative stress via release of glutathionylated peroxiredoxin-2, which acts as a danger signal. Proc Natl Acad Sci USA 111, 12157\u201312162 (2014).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1038\/ni.1633","article-title":"Superoxide dismutase 1 regulates caspase-1 and endotoxic shock","volume":"9","author":"Meissner F","year":"2008","unstructured":"F Meissner, K Molawi, A Zychlinsky, Superoxide dismutase 1 regulates caspase-1 and endotoxic shock. Nat Immunol 9, 866\u2013872 (2008).","journal-title":"Nat Immunol"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/path.2287","article-title":"TNF-mediated inflammatory disease","volume":"214","author":"Bradley JR","year":"2008","unstructured":"JR Bradley, TNF-mediated inflammatory disease. J Pathol 214, 149\u2013160 (2008).","journal-title":"J Pathol"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"R247","DOI":"10.1186\/ar4090","article-title":"Murine Borrelia arthritis is highly dependent on ASC and caspase-1, but independent of NLRP3","volume":"14","author":"Oosting M","year":"2012","unstructured":"M Oosting, , Murine Borrelia arthritis is highly dependent on ASC and caspase-1, but independent of NLRP3. 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