tetano
Editor, Senior Moderator
J Immunol. 2014 Jul 23. pii: 1303339. [Epub ahead of print]
Macrophage- and Neutrophil-Derived TNF-α Instructs Skin Langerhans Cells To Prime Antiviral Immune Responses.
Epaulard O1, Adam L2, Poux C2, Zurawski G3, Salabert N2, Rosenbaum P2, Dereuddre-Bosquet N2, Zurawski S3, Flamar AL3, Oh S4, Romain G2, Chapon C2, Banchereau J3, L?vy Y5, Le Grand R2, Martinon F6.
Author information
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 ? 2014 by The American Association of Immunologists, Inc.
PMID:
25057007
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25057007
Macrophage- and Neutrophil-Derived TNF-α Instructs Skin Langerhans Cells To Prime Antiviral Immune Responses.
Epaulard O1, Adam L2, Poux C2, Zurawski G3, Salabert N2, Rosenbaum P2, Dereuddre-Bosquet N2, Zurawski S3, Flamar AL3, Oh S4, Romain G2, Chapon C2, Banchereau J3, L?vy Y5, Le Grand R2, Martinon F6.
Author information
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 ? 2014 by The American Association of Immunologists, Inc.
PMID:
25057007
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25057007