Klebsiella pneumoniae‐triggered DC recruit human NK cells in a CCR5‐dependent manner leading to increased CCL19‐responsiveness and activation of NK cells |
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Authors: | Catharina H. M. J. Van Elssen Joris Vanderlocht Peter W. H. Frings Birgit L. M. G. Senden‐Gijsbers Melanie C. A. Schnijderberg Michel van Gelder Bob Meek Christine Libon Guido Ferlazzo Wilfred T. V. Germeraad Gerard M. J. Bos |
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Affiliation: | 1. Department of Internal Medicine, Division of Hematology, Maastricht University Medical Center+, Maastricht, The Netherlands;2. PharmaCell BV, Maastricht, The Netherlands;3. Pierre Fabre Research Institute, Ramonville, France;4. Department of Human Pathology, School of Medicine, University of Messina, Messina, Italy |
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Abstract: | Besides their role in destruction of altered self‐cells, NK cells have been shown to potentiate T‐cell responses by interacting with DC. To take advantage of NK–DC crosstalk in therapeutic DC‐based vaccination for infectious diseases and cancer, it is essential to understand the biology of this crosstalk. We aimed to elucidate the in vitro mechanisms responsible for NK‐cell recruitment and activation by DC during infection. To mimic bacterial infection, DC were exposed to a membrane fraction of Klebsiella pneumoniae, which triggers TLR2/4. DC matured with these bacterial fragments can actively recruit NK cells in a CCR5‐dependent manner. An additional mechanism of DC‐induced NK‐cell recruitment is characterized by the induction of CCR7 expression on CD56dimCD16+ NK cells after physical contact with membrane fraction of K. pneumoniae‐matured DC, resulting in an enhanced migratory responsiveness to the lymph node‐associated chemokine CCL19. Bacterial fragment‐matured DC do not only mediate NK‐cell migration but also meet the prerequisites needed for augmentation of NK‐cell cytotoxicity and IFN‐γ production, the latter of which contributes to Th1 polarization. |
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Keywords: | CCR5 CCR7 NK– DC interaction Th1 polarization |
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