Adriana Marques1, Ira Schwartz2, Gary P Wormser3, Yanmei Wang4, Ronald L Hornung4, Cumhur Y Demirkale5, Peter J Munson5, Siu-Ping Turk1, Carla Williams4, Chyi-Chia Richard Lee6, Jun Yang7, Mary M Petzke2. 1. Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. 2. Department of Microbiology and Immunology, Valhalla. 3. Division of Infectious Diseases, Department of Medicine, New York Medical College, Valhalla. 4. Clinical Services Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Maryland. 5. Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, Maryland. 6. Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. 7. Laboratory of Human Retrovirology and Immunoinformatics, Leidos Biomedical Research, Inc. Frederick National Laboratory for Cancer Research, Maryland.
Abstract
Background: The most common clinical manifestation of early Lyme disease is the erythema migrans (EM) skin lesion that develops at the tick bite site typically between 7 and 14 days after infection with Borreliella burgdorferi. The host-pathogen interactions that occur in the skin may have a critical role in determining outcome of infection. Methods: Gene arrays were used to characterize the global transcriptional alterations in skin biopsy samples of EM lesions from untreated adult patients with Lyme disease in comparison to controls. Results: The transcriptional pattern in EM biopsies consisted of 254 differentially regulated genes (180 induced and 74 repressed) characterized by the induction of chemokines, cytokines, Toll-like receptors, antimicrobial peptides, monocytoid cell activation markers, and numerous genes annotated as interferon (IFN)-inducible. The IFN-inducible genes included 3 transcripts involved in tryptophan catabolism (IDO1, KMO, KYNU) that play a pivotal role in immune evasion by certain other microbial pathogens by driving the differentiation of regulatory T cells. Conclusions: This is the first study to globally assess the human skin transcriptional response during early Lyme disease. Borreliella burgdorferi elicits a predominant IFN signature in the EM lesion, suggesting a potential mechanism for spirochetal dissemination via IDO1-mediated localized immunosuppression.
Background: The most common clinical manifestation of early Lyme disease is the erythema migrans (EM) skin lesion that develops at the tick bite site typically between 7 and 14 days after infection with Borreliella burgdorferi. The host-pathogen interactions that occur in the skin may have a critical role in determining outcome of infection. Methods: Gene arrays were used to characterize the global transcriptional alterations in skin biopsy samples of EM lesions from untreated adult patients with Lyme disease in comparison to controls. Results: The transcriptional pattern in EM biopsies consisted of 254 differentially regulated genes (180 induced and 74 repressed) characterized by the induction of chemokines, cytokines, Toll-like receptors, antimicrobial peptides, monocytoid cell activation markers, and numerous genes annotated as interferon (IFN)-inducible. The IFN-inducible genes included 3 transcripts involved in tryptophan catabolism (IDO1, KMO, KYNU) that play a pivotal role in immune evasion by certain other microbial pathogens by driving the differentiation of regulatory T cells. Conclusions: This is the first study to globally assess the human skin transcriptional response during early Lyme disease. Borreliella burgdorferi elicits a predominant IFN signature in the EM lesion, suggesting a potential mechanism for spirochetal dissemination via IDO1-mediated localized immunosuppression.
Authors: Xiaoli Jiao; Brad T Sherman; Da Wei Huang; Robert Stephens; Michael W Baseler; H Clifford Lane; Richard A Lempicki Journal: Bioinformatics Date: 2012-04-27 Impact factor: 6.937
Authors: Robert B Lochhead; Sheila L Arvikar; John M Aversa; Ruslan I Sadreyev; Klemen Strle; Allen C Steere Journal: Cell Microbiol Date: 2018-10-17 Impact factor: 3.715
Authors: Emily M Siebers; Elizabeth S Liedhegner; Michael W Lawlor; Ronald F Schell; Dean T Nardelli Journal: Infect Immun Date: 2020-10-19 Impact factor: 3.441
Authors: Bryna L Fitzgerald; Claudia R Molins; M Nurul Islam; Barbara Graham; Petronella R Hove; Gary P Wormser; Linden Hu; Laura V Ashton; John T Belisle Journal: J Proteome Res Date: 2020-01-09 Impact factor: 4.466
Authors: Angelique N Besold; Edward M Culbertson; Lily Nam; Ryan P Hobbs; Alisa Boyko; C Noel Maxwell; Walter J Chazin; Adriana R Marques; Valeria C Culotta Journal: Metallomics Date: 2018-12-12 Impact factor: 4.526
Authors: Adoracion Pegalajar-Jurado; Bryna L Fitzgerald; M Nurul Islam; John T Belisle; Gary P Wormser; Kathlene S Waller; Laura V Ashton; Kristofor J Webb; Mark J Delorey; Rebecca J Clark; Claudia R Molins Journal: Sci Rep Date: 2018-08-15 Impact factor: 4.379
Authors: Ruoyi Jiang; Hailong Meng; Khadir Raddassi; Ira Fleming; Kenneth B Hoehn; Kenneth R Dardick; Alexia A Belperron; Ruth R Montgomery; Alex K Shalek; David A Hafler; Steven H Kleinstein; Linda K Bockenstedt Journal: JCI Insight Date: 2021-06-22
Authors: Robert B Lochhead; Klemen Strle; Sheila L Arvikar; Janis J Weis; Allen C Steere Journal: Nat Rev Rheumatol Date: 2021-07-05 Impact factor: 32.286
Authors: Mary M Petzke; Konstantin Volyanskyy; Yong Mao; Byron Arevalo; Raphael Zohn; Johanna Quituisaca; Gary P Wormser; Nevenka Dimitrova; Ira Schwartz Journal: mBio Date: 2020-03-17 Impact factor: 7.867