Open AccessBorrelia burgdorferi potently activates bone marrow‐derived conventional dendritic cells for production of IL‐23 required for IL‐17 release by T cells
Author(s) -
Knauer Jens,
Siegemund Sabine,
Müller Uwe,
AlRobaiy Samiya,
Kastelein Robert A.,
Alber Gottfried,
Straubinger Reinhard K.
Publication year - 2007
Publication title -
fems immunology & medical microbiology
Language(s) - English
Resource type - Journals
eISSN - 1574-695X
pISSN - 0928-8244
DOI - 10.1111/j.1574-695x.2006.00210.x
Subject(s) - biology , borrelia burgdorferi , immunology , proinflammatory cytokine , cytokine , dendritic cell , bone marrow , chemokine , microbiology and biotechnology , inflammation , immune system , antibody
Lyme borreliosis is characterized by cellular inflammatory responses at multiple body sites. Recently, an association of interleukin‐17 (IL–17) and Lyme arthritis was suggested. In this context, it is of special interest that the heterodimeric cytokine IL‐23 can act on T cells and initiate the up‐regulation of effector cytokines such as IL‐17. To determine the role of this specific cytokine cascade for the induction of subsequently induced proinflammatory events we developed an in vitro system to investigate the IL‐23‐inducing capacity of Borrelia burgdorferi and the potential of the spirochete for inducing the IL‐23/IL‐17 axis. We used cells derived from mice deficient for IL‐23 or IL‐12 only or deficient for both IL‐12 and IL‐23 to define precisely the function of these cytokines. Experiments with bone marrow‐derived dendritic cells (BMDC) identified these cells as sources for IL‐23 but not for IL‐12 after B. burgdorferi exposure. Subsequent investigations with T cell‐depleted splenocyte fractions revealed a tight IL‐23/IL‐17 axis in response to the spirochetes. Monoclonal antibodies that block IL‐23 showed further that BMDC‐derived IL‐23 was required for production of IL‐17 in this experimental model. These in vitro data describing a spirochete‐induced release of IL‐23 may help to define IL‐17‐dependent inflammatory responses in the disease.