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Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 J+Immunol 2014 ; 193 (5): 2416-26 Nephropedia Template TP
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Macrophage- and Neutrophil-Derived TNF-? Instructs Skin Langerhans Cells to Prime Antiviral Immune Responses #MMPMID25057007
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
J Immunol 2014[Sep]; 193 (5): 2416-26 PMID25057007show ga
Dendritic cells (DCs) are major antigen presenting cells that can efficiently prime immune responses. However, the roles of skin resident Langerhans cells (LCs) in eliciting immune responses have not been fully understood. We here demonstrate for the first time that LCs in cynomolgus macaque skin are capable of inducing antiviral-specific immune responses in vivo. Targeting HIV-Gag or influenza hemagglutinin antigens to skin LCs using recombinant fusion proteins of anti-Langerin antibody and antigens resulted in the induction of the viral antigen-specific responses. We further demonstrated that such antigen-specific immune responses elicited by skin LCs were greatly enhanced by TLR ligands (TLR-Ls), polyriboinosinic polyribocytidylic acid (poly(I:C)) and R848. These enhancements were not due to the direct actions of TLR-Ls 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.