NDLI: Macrophage- and neutrophil-derived TNF- instructs skin langerhans cells to prime antiviral immune responses.

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Macrophage- and neutrophil-derived TNF- instructs skin langerhans cells to prime antiviral immune responses.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Zurawski, Gerard Martinon, Frédéric Epaulard, Olivier Romain, Gabrielle Le Grand, Roger Lévy, Yves Flamar, Anne-Laure Oh, Sangkon Adam, Lucille Salabert, Nina Chapon, Catherine Dereuddre-Bosquet, Nathalie Poux, Candice Rosenbaum, Pierre Banchereau, Jacques Zurawski, Sandra
Description	Author Affiliation: Epaulard O ( French Alternative Energies and Atomic Energy Commission, Division of Immuno-Virology, Institute for Emerging Diseases and Innovative Therapies, Infectious Diseases Models for Innovative Therapies Center, 92265 Fontenay-aux-Roses, France); Adam L ( French Alternative Energies and Atomic Energy Commission, Division of Immuno-Virology, Institute for Emerging Diseases and Innovative Therapies, Infectious Diseases Models for Innovative Therapies Center, 92265 Fontenay-aux-Roses, France); Poux C ( French Alternative Energies and Atomic Energy Commission, Division of Immuno-Virology, Institute for Emerging Diseases and Innovative Therapies, Infectious Diseases Models for Innovative Therapies Center, 92265 Fontenay-aux-Roses, France); Zurawski G ( Vaccine Research Institute, 94010 Créteil, France); Salabert N ( French Alternative Energies and Atomic Energy Commission, Division of Immuno-Virology, Institute for Emerging Diseases and Innovative Therapies, Infectious Diseases Models for Innovative Therapies Center, 92265 Fontenay-aux-Roses, France); Rosenbaum P ( French Alternative Energies and Atomic Energy Commission, Division of Immuno-Virology, Institute for Emerging Diseases and Innovative Therapies, Infectious Diseases Models for Innovative Therapies Center, 92265 Fontenay-aux-Roses, France); Dereuddre-Bosquet N ( French Alternative Energies and Atomic Energy Commission, Division of Immuno-Virology, Institute for Emerging Diseases and Innovative Therapies, Infectious Diseases Models for Innovative Therapies Center, 92265 Fontenay-aux-Roses, France); Zurawski S ( Vaccine Research Institute, 94010 Créteil, France); Flamar AL ( Vaccine Research Institute, 94010 Créteil, France); Oh S ( Baylor Institute for Immunology Research, Dallas, TX 75204); Romain G ( French Alternative Energies and Atomic Energy Commission, Division of Immuno-Virology, Institute for Emerging Diseases and Innovative Therapies, Infectious Diseases Models for Innovative Therapies Center, 92265 Fontenay-aux-Roses, France); Chapon C ( French Alternative Energies and Atomic Energy Commission, Division of Immuno-Virology, Institute for Emerging Diseases and Innovative Therapies, Infectious Diseases Models for Innovative Therapies Center, 92265 Fontenay-aux-Roses, France); Banchereau J ( Vaccine Research Institute, 94010 Créteil, France); Lévy Y ( Vaccine Research Institute, 94010 Créteil, France); Le Grand R ( French Alternative Energies and Atomic Energy Commission, Division of Immuno-Virology, Institute for Emerging Diseases and Innovative Therapies, Infectious Diseases Models for Innovative Therapies Center, 92265 Fontenay-aux-Roses, France); Martinon F ( French Alternative Energies and Atomic Energy Commission, Division of Immuno-Virology, Institute for Emerging Diseases and Innovative Therapies, Infectious Diseases Models for Innovative Therapies Center, 92265 Fontenay-aux-Roses, France)
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- 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- 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.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1303339
Journal	The Journal of Immunology
Issue Number	5
Volume Number	193
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-09-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Hiv-1 Immunology Hemagglutinin Glycoproteins, Influenza Virus Pharmacology Influenza A Virus Langerhans Cells Skin Tumor Necrosis Factor-alpha Gag Gene Products, Human Immunodeficiency Virus Adaptive Immunity Drug Effects Physiology Animals Imidazoles Macaca Mulatta Macrophages Neutrophils Poly I Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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Macrophage- and Neutrophil-Derived TNF-α Instructs Skin Langerhans Cells to Prime Antiviral Immune Responses

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Macrophage- and neutrophil-derived TNF- instructs skin langerhans cells to prime antiviral immune responses.

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