TY - JOUR
T1 - Klebsiella pneumoniae-triggered DC recruit human NK cells in a CCR5-dependent manner leading to increased CCL19-responsiveness and activation of NK cells
AU - Van Elssen, Catharina H. M. J.
AU - Vanderlocht, Joris
AU - Frings, Peter W. H.
AU - Senden-Gijsbers, Birgit L. M. G.
AU - Schnijderberg, Melanie C. A.
AU - van Gelder, Michel
AU - Meek, Bob
AU - Libon, Christine
AU - Ferlazzo, Guido
AU - Germeraad, Wilfred T. V.
AU - Bos, Gerard M. J.
PY - 2010/11
Y1 - 2010/11
N2 - 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-gamma production, the latter of which contributes to Th1 polarization.
AB - 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-gamma production, the latter of which contributes to Th1 polarization.
KW - CCR5
KW - CCR7
KW - NK-DC interaction
KW - Th1 polarization
U2 - 10.1002/eji.201040496
DO - 10.1002/eji.201040496
M3 - Article
C2 - 20865789
SN - 0014-2980
VL - 40
SP - 3138
EP - 3149
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 11
ER -