Autophagy suppresses host adaptive immune responses toward Borrelia burgdorferi

Kathrin Buffen, Marije Oosting, Yang Li, Thirumala-Devi Kanneganti, Mihai G. Netea, Leo A. B. Joosten*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    10 Citations (Scopus)

    Abstract

    Inhibition of autophagy increases the severity of murine Lyme arthritis and human adaptive immune responses against B. burgdorferi. We have previously demonstrated that inhibition of autophagy increased the Borrelia burgdorferi induced innate cytokine production in vitro, but little is known regarding the effect of autophagy on in vivo models of Borrelia infection. Here, we showed that ATG7-deficient mice that were intra-articular injected with Borrelia spirochetes displayed increased joint swelling, cell influx, and enhanced interleukin-1 and interleukin-6 production by inflamed synovial tissue. Because both interleukin-1 and interleukin-6 are linked to the development of adaptive immune responses, we examine the function of autophagy on Borrelia induced adaptive immunity. Human peripheral blood mononuclear cells treated with autophagy inhibitors showed an increase in interleukin-17, interleukin-22, and interferon- production in response to exposure to Borrelia burgdorferi. Increased IL-17 production was dependent on IL-1 release but, interestingly, not on interleukin-23 production. In addition, cytokine quantitative trait loci in ATG9B modulate the Borrelia induced interleukin-17 production. Because high levels of IL-17 have been found in patients with confirmed, severe, chronic borreliosis, we propose that the modulation of autophagy may be a potential target for anti-inflammatory therapy in patients with persistent Lyme disease.

    Original languageEnglish
    Pages (from-to)589-598
    Number of pages10
    JournalJournal of Leukocyte Biology
    Volume100
    Issue number3
    DOIs
    Publication statusPublished - Sept-2016

    Keywords

    • IL-17
    • IL-23
    • Lyme disease
    • LYME-DISEASE
    • RECEPTOR ANTAGONIST
    • ERYTHEMA MIGRANS
    • T-CELLS
    • ARTHRITIS
    • IL-1-BETA
    • MICE
    • INTERLEUKIN-23
    • INFLAMMATION

    Fingerprint

    Dive into the research topics of 'Autophagy suppresses host adaptive immune responses toward Borrelia burgdorferi'. Together they form a unique fingerprint.

    Cite this