NYMC Faculty Publications

Title

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

Document Type

Article

Publication Date

December 2017

Department

Microbiology and Immunology

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 following 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 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. 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 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. Conclusion: 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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