MicroRNA-146a Provides Feedback Regulation of Lyme Arthritis but Not Carditis during Infection with

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Lyme Disease is caused by infection with the bacteria Borrelia burgdorferi, is transmitted through infected deer ticks (Ixodes scapularis), and often leads to arthritis that can persist, even after antibiotic treatment. Here, we have identified a microRNA that is critical in modulating Lyme arthritis, but not carditis. This microRNA, miR-146a, is a negative regulator of NF-κB signaling, known to be important in host defense against pathogens, and long suspected to play a role in Lyme arthritis development. Mice lacking miR-146a develop more severe arthritis and show signs of hyperactive NF-κB activation during the persistent phase of infection. Heart manifestations of disease were not altered. Furthermore, this severe arthritis is independent of host defense, since these mice are better able to clear invading bacteria in joints, and bacterial numbers are similar in heart and ear tissue. We identified TRAF6 as an important target of miR-146a-mediated NF-κB regulation of pro-inflammatory cytokines IL-6 and IL-1β, as well as chemokines CXCL1 and CXCL2. Our data demonstrate the importance of maintaining appropriate regulation of amplitude and resolution of NF-κB activation during Borrelia burgdorferi infection, and provide a novel model for elucidating the role of NF-κB in Lyme arthritis development, independent of effect on host defense.

Vyšlo v časopise: MicroRNA-146a Provides Feedback Regulation of Lyme Arthritis but Not Carditis during Infection with. PLoS Pathog 10(6): e32767. doi:10.1371/journal.ppat.1004212
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004212

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