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
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-gamma but to a large part dependent on caspase-1 and IL-1 bioactivity derived from monocytes. In fact, IL-1beta 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.
|Author:||Malte Bachmann, Katharina Horn, Ina Rudloff, Itamar Goren, Martin Holdener, Urs Christen, Nicole Darsow, Klaus-Peter Hunfeld, Ulrike Koehl, Peter Kind, Josef Martin Pfeilschifter, Peter Kraiczy, Heiko Mühl|
|Parent Title (English):||PLoS pathogens|
|Place of publication:||Lawrence, Kan.|
|Date of Publication (online):||09.09.2010|
|Date of first Publication:||09.09.2010|
|Publishing Institution:||Univ.-Bibliothek Frankfurt am Main|
|Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit|
|Dewey Decimal Classification:||610 Medizin und Gesundheit|
Copyright: © 2010 Bachmann et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
|Licence (German):||Creative Commons - Namensnennung 3.0|