Functional and Genomic Architecture of Borrelia burgdorferi-Induced Cytokine Responses in Humans
until further notice
SourceCell Host & Microbe, 20, 6, (2016), pp. 822-833
Article / Letter to editor
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Cell Host & Microbe
SubjectRadboudumc 4: lnfectious Diseases and Global Health RIHS: Radboud Institute for Health Sciences; Radboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 9: Rare cancers RIMLS: Radboud Institute for Molecular Life Sciences
Despite the importance of immune variation for the symptoms and outcome of Lyme disease, the factors influencing cytokine production during infection with the causal pathogen Borrelia burgdorferi remain poorly understood. Borrelia infection-induced monocyte- and T cell-derived cytokines were profiled in peripheral blood from two healthy human cohorts of Western Europeans from the Human Functional Genomics Project. Both non-genetic and genetic host factors were found to influence Borrelia-induced cytokine responses. Age strongly impaired IL-22 responses, and genetic studies identified several independent QTLs that impact Borrelia-induced cytokine production. Genetic, transcriptomic, and functional validation studies revealed an important role for HIF-1alpha-mediated glycolysis in the cytokine response to Borrelia. HIF-1alpha pathway activation and increase in glycolysis-derived lactate was confirmed in Lyme disease patients. In conclusion, functional genomics approaches reveal the architecture of cytokine production induced by Borrelia infection of human primary leukocytes and suggest a connection between cellular glucose metabolism and Borrelia-induced cytokine production.
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