Transcriptome Assessment of Erythema Migrans Skin Lesions in Patients with Early Lyme Disease Reveals Predominant Interferon Signaling

Author:

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
Author Address

Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Department of Microbiology and Immunology, New York Medical College, Valhalla, New York, USA., Division of Infectious Diseases, Department of Medicine, New York Medical College, Valhalla, New York, USA., Clinical Services Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA., Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, Maryland, USA., Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA., Laboratory of Human Retrovirology and Immunoinformatics, Leidos Biomedical Research, Inc. Frederick National Laboratory for Cancer Research.,

Abstract:

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 following infection with Borreliella burgdorferi. The host-pathogen interactions that occur in the skin may have a critical role in determining outcome of infection. Gene arrays were utilized to characterize the global transcriptional alterations in skin biopsy samples of EM lesions from untreated adult patients with Lyme disease in comparison to controls. 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 three 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. This is the first study to globally assess the human skin transcriptional response during early Lyme disease. B. burgdorferi elicits a predominant IFN signature in the EM lesion, suggesting a potential mechanism for spirochetal dissemination via IDO1-mediated localized immunosuppression.

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