Early Production of IL-22 but Not IL-17 by Peripheral Blood Mononuclear Cells Exposed to live Borrelia burgdorferi: The Role of Monocytes and Interleukin-1

PLoS Pathogens

Josef Pfeilschifter¹  Ulrike Koehl²  Klaus-Peter Hunfeld³  Heiko Mühl³  Peter Kind⁴  Nicole Darsow⁵  Katharina Horn⁵  Itamar Goren⁵  Urs Christen⁵  Ina Rudloff⁵  Malte Bachmann⁵  Martin Holdener⁵  Peter Kraiczy⁵ 

[1] Dermatohistological Laboratory Offenbach, Offenbach, Germany;Institute for Laboratory Medicine, North West Medical Centre, Frankfurt, Germany;Institute of Medical Microbiology and Infection Control, University Hospital Goethe University Frankfurt, Frankfurt, Germany;Pediatric Hematology and Oncology, University Hospital Goethe-University Frankfurt, Frankfurt, Germany;pharmazentrum frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt, Germany

关键词: Borrelia burgdorferi;    T cells;    Cytokines;    Secretion;    Cytotoxic T cells;    Spirochetes;    Enzyme-linked immunoassays;    Monocytes;   

DOI  :  10.1371/journal.ppat.1001144

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

If insufficiently treated, Lyme borreliosis can evolve into an inflammatory disorder affecting skin, joints, and the CNS. Early innate immunity may determine host responses targeting infection. Thus, we sought to characterize the immediate cytokine storm associated with exposure of PBMC to moderate levels of live Borrelia burgdorferi. Since Th17 cytokines are connected to host defense against extracellular bacteria, we focused on interleukin (IL)-17 and IL-22. Here, we report that, despite induction of inflammatory cytokines including IL-23, IL-17 remained barely detectable in response to B. burgdorferi. In contrast, T cell-dependent expression of IL-22 became evident within 10 h of exposure to the spirochetes. This dichotomy was unrelated to interferon-γ but to a large part dependent on caspase-1 and IL-1 bioactivity derived from monocytes. In fact, IL-1β as a single stimulus induced IL-22 but not IL-17. Neutrophils display antibacterial activity against B. burgdorferi, particularly when opsonized by antibodies. Since neutrophilic inflammation, indicative of IL-17 bioactivity, is scarcely observed in Erythema migrans, a manifestation of skin inflammation after infection, protective and antibacterial properties of IL-22 may close this gap and serve essential functions in the initial phase of spirochete infection.

【 授权许可】

CC BY