Klebsiella pneumoniae-triggered DC recruit human NK cells in a CCR5-dependent manner leading to increased CCL19-responsiveness and activation of NK cells.
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 CD56(dim) CD16(+) 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.
Van Elssen
Catharina H M J
CH
Department of Internal Medicine, Division of Hematology, Maastricht University Medical Center, Maastricht, The Netherlands. J.vanelssen@immuno.unimaas.nl
Vanderlocht
Joris
J
Frings
Peter W H
PW
Senden-Gijsbers
Birgit L M G
BL
Schnijderberg
Melanie C A
MC
van Gelder
Michel
M
Meek
Bob
B
Libon
Christine
C
Ferlazzo
Guido
G
Germeraad
Wilfred T V
WT
Bos
Gerard M J
GM
D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D054415:Chemokine CCL19 / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D007710:Klebsiella Infections / Q000276:immunology*; D007711:Klebsiella pneumoniae / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D019713:Receptors, CCR5 / Q000276:immunology*; D054400:Receptors, CCR7 / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology
C515460:CCL19 protein, human; C515370:CCR7 protein, human; D054415:Chemokine CCL19; D019713:Receptors, CCR5; D054400:Receptors, CCR7; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D007371:Interferon-gamma