Transcriptome Assessment of Erythema Migrans Skin Lesions in Patients With Early Lyme Disease Reveals Predominant Interferon Signaling. (1st November 2017)

• Record Type: Journal Article
• Authors: Marques, Adriana; Schwartz, Ira; Wormser, Gary P; Wang, Yanmei; Hornung, Ronald L; Demirkale, Cumhur Y; Munson, Peter J; Turk, Siu-Ping; Williams, Carla; Lee, Chyi-Chia Richard; Yang, Jun; Petzke, Mary M
• Is Part Of: Journal of infectious diseases. Volume 217:Number 1(2018)
• Page Start: 158
• Page End: 167
• Publication Date: 2017-11-01
• Subjects: skin -- interferon -- Treg -- Lyme disease; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jix563
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract : Early cutaneous Lyme disease is characterized by a predominant interferon signature. Immune activation and spirochete phagocytosis is counterbalanced by the immunosuppressive effects of tryptophan catabolism. The capacity of Borrelia burgdorferi to manipulate these opposing pathways may determine infection outcome. 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.