Macrophage-and neutrophil-derived TNF-α instructs skin Langerhans cells to prime antiviral immune responses

Olivier Epaulard, Lucille Adam, Candice Poux, Gerard Zurawski, Nina Salabert, Pierre Rosenbaum, Nathalie Dereuddre-Bosquet, Sandra Zurawski, Anne Laure Flamar, SangKon Oh, Gabrielle Romain, Catherine Chapon, Jacques Banchereau, Yves Lévy, Roger Le Grand, Frédéric Martinon

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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. Understanding the importance of local immune networks will help us to design new and effective vaccines against microbial pathogens Copyright

Original languageEnglish (US)
Pages (from-to)2416-2426
Number of pages11
JournalJournal of Immunology
Volume193
Issue number5
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Langerhans Cells
Antiviral Agents
Neutrophils
Macrophages
Skin
resiquimod
Recombinant Fusion Proteins
Ligands
Neutrophil Infiltration
Hemagglutinins
Macaca
Adaptive Immunity
Epidermis
Dendritic Cells
Human Influenza
Cell Movement
Vaccines
HIV

ASJC Scopus subject areas

  • Immunology

Cite this

Epaulard, O., Adam, L., Poux, C., Zurawski, G., Salabert, N., Rosenbaum, P., ... Martinon, F. (2014). Macrophage-and neutrophil-derived TNF-α instructs skin Langerhans cells to prime antiviral immune responses. Journal of Immunology, 193(5), 2416-2426. https://doi.org/10.4049/jimmunol.1303339

Macrophage-and neutrophil-derived TNF-α instructs skin Langerhans cells to prime antiviral immune responses. / Epaulard, Olivier; Adam, Lucille; Poux, Candice; Zurawski, Gerard; Salabert, Nina; Rosenbaum, Pierre; Dereuddre-Bosquet, Nathalie; Zurawski, Sandra; Flamar, Anne Laure; Oh, SangKon; Romain, Gabrielle; Chapon, Catherine; Banchereau, Jacques; Lévy, Yves; Le Grand, Roger; Martinon, Frédéric.

In: Journal of Immunology, Vol. 193, No. 5, 01.01.2014, p. 2416-2426.

Research output: Contribution to journalArticle

Epaulard, O, Adam, L, Poux, C, Zurawski, G, Salabert, N, Rosenbaum, P, Dereuddre-Bosquet, N, Zurawski, S, Flamar, AL, Oh, S, Romain, G, Chapon, C, Banchereau, J, Lévy, Y, Le Grand, R & Martinon, F 2014, 'Macrophage-and neutrophil-derived TNF-α instructs skin Langerhans cells to prime antiviral immune responses', Journal of Immunology, vol. 193, no. 5, pp. 2416-2426. https://doi.org/10.4049/jimmunol.1303339
Epaulard, Olivier ; Adam, Lucille ; Poux, Candice ; Zurawski, Gerard ; Salabert, Nina ; Rosenbaum, Pierre ; Dereuddre-Bosquet, Nathalie ; Zurawski, Sandra ; Flamar, Anne Laure ; Oh, SangKon ; Romain, Gabrielle ; Chapon, Catherine ; Banchereau, Jacques ; Lévy, Yves ; Le Grand, Roger ; Martinon, Frédéric. / Macrophage-and neutrophil-derived TNF-α instructs skin Langerhans cells to prime antiviral immune responses. In: Journal of Immunology. 2014 ; Vol. 193, No. 5. pp. 2416-2426.
@article{94fdcb313d4a47998bbfeb96dda59723,
title = "Macrophage-and neutrophil-derived TNF-α instructs skin Langerhans cells to prime antiviral immune responses",
abstract = "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. Understanding the importance of local immune networks will help us to design new and effective vaccines against microbial pathogens Copyright",
author = "Olivier Epaulard and Lucille Adam and Candice Poux and Gerard Zurawski and Nina Salabert and Pierre Rosenbaum and Nathalie Dereuddre-Bosquet and Sandra Zurawski and Flamar, {Anne Laure} and SangKon Oh and Gabrielle Romain and Catherine Chapon and Jacques Banchereau and Yves L{\'e}vy and {Le Grand}, Roger and Fr{\'e}d{\'e}ric Martinon",
year = "2014",
month = "1",
day = "1",
doi = "10.4049/jimmunol.1303339",
language = "English (US)",
volume = "193",
pages = "2416--2426",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "5",

}

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

PY - 2014/1/1

Y1 - 2014/1/1

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. Understanding the importance of local immune networks will help us to design new and effective vaccines against microbial pathogens Copyright

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. Understanding the importance of local immune networks will help us to design new and effective vaccines against microbial pathogens Copyright

UR - http://www.scopus.com/inward/record.url?scp=84907033468&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907033468&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1303339

DO - 10.4049/jimmunol.1303339

M3 - Article

C2 - 25057007

AN - SCOPUS:84907033468

VL - 193

SP - 2416

EP - 2426

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 5

ER -