TY - JOUR
T1 - Macrophage-and neutrophil-derived TNF-α instructs skin Langerhans cells to prime antiviral immune responses
AU - Epaulard, Olivier
AU - Adam, Lucille
AU - Poux, Candice
AU - Zurawski, Gerard
AU - Salabert, Nina
AU - Rosenbaum, Pierre
AU - Dereuddre-Bosquet, Nathalie
AU - Zurawski, Sandra
AU - Flamar, Anne Laure
AU - Oh, Sangkon
AU - Romain, Gabrielle
AU - Chapon, Catherine
AU - Banchereau, Jacques
AU - Lévy, Yves
AU - Le Grand, Roger
AU - Martinon, Frédéric
N1 - Publisher Copyright:
© 2014 by The American Association of Immunologists, Inc.
PY - 2014/9/1
Y1 - 2014/9/1
N2 - Dendritic cells are major APCs that can efficiently prime immune responses. However, the roles of skin-resident Langerhans cells (LCs) in eliciting immune responses have not been fully understood. In this study, we demonstrate for the first time, to our knowledge, that LCs in cynomolgus macaque skin are capable of inducing antiviral-specific immune responses in vivo. Targeting HIV-Gag or influenza hemagglutinin Ags to skin LCs using recombinant fusion proteins of anti-Langerin Ab and Ags resulted in the induction of the viral Ag-specific responses. We further demonstrated that such Ag-specific immune responses elicited by skin LCs were greatly enhanced by TLR ligands, polyriboinosinic polyribocytidylic acid, and R848. These enhancements were not due to the direct actions of TLR ligands on LCs, but mainly dependent on TNF-α secreted from macrophages and neutrophils recruited to local tissues. Skin LC activation and migration out of the epidermis are associated with macrophage and neutrophil infiltration into the tissues. More importantly, blocking TNF-α abrogated the activation and migration of skin LCs. This study highlights that the cross-talk between innate immune cells in local tissues is an important component for the establishment of adaptive immunity.
AB - Dendritic cells are major APCs that can efficiently prime immune responses. However, the roles of skin-resident Langerhans cells (LCs) in eliciting immune responses have not been fully understood. In this study, we demonstrate for the first time, to our knowledge, that LCs in cynomolgus macaque skin are capable of inducing antiviral-specific immune responses in vivo. Targeting HIV-Gag or influenza hemagglutinin Ags to skin LCs using recombinant fusion proteins of anti-Langerin Ab and Ags resulted in the induction of the viral Ag-specific responses. We further demonstrated that such Ag-specific immune responses elicited by skin LCs were greatly enhanced by TLR ligands, polyriboinosinic polyribocytidylic acid, and R848. These enhancements were not due to the direct actions of TLR ligands on LCs, but mainly dependent on TNF-α secreted from macrophages and neutrophils recruited to local tissues. Skin LC activation and migration out of the epidermis are associated with macrophage and neutrophil infiltration into the tissues. More importantly, blocking TNF-α abrogated the activation and migration of skin LCs. This study highlights that the cross-talk between innate immune cells in local tissues is an important component for the establishment of adaptive immunity.
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U2 - 10.4049/jimmunol.1303339
DO - 10.4049/jimmunol.1303339
M3 - Article
C2 - 25057007
AN - SCOPUS:84907033468
SN - 0022-1767
VL - 193
SP - 2416
EP - 2426
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -