Autophagy suppresses host adaptive immune responses toward Borrelia burgdorferi. Issue 3 (21st April 2016)

• Record Type: Journal Article
• Authors: Buffen, Kathrin; Oosting, Marije; Li, Yang; Kanneganti, Thirumala‐Devi; Netea, Mihai G.; Joosten, Leo A. B.
• Is Part Of: Journal of leukocyte biology. Volume 100:Issue 3(2016)
• Page Start: 589
• Page End: 598
• Publication Date: 2016-04-21
• Subjects: IL‐17 -- IL‐23 -- Lyme disease; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.4A0715-331R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : Inhibition of autophagy increases the severity of murine Lyme arthritis and human adaptive immune responses against B. burgdorferi . Abstract : 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‐1β and interleukin‐6 production by inflamed synovial tissue. Because both interleukin‐1β 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‐γ production in response to exposure to Borrelia burgdorferi. Increased IL‐17 production was dependent on IL‐1β 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.