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Macrophages transfer antigens to dendritic cells by releasing exosomes containing dead‐cell‐associated antigens partially through a ceramide‐dependent pathway to enhance CD 4 + T‐cell responses
Author(s) -
Xu Yingping,
Liu Yi,
Yang Chunqing,
Kang Li,
Wang Meixiang,
Hu Jingxia,
He Hao,
Song Wengang,
Tang Hua
Publication year - 2016
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12630
Subject(s) - microvesicles , microbiology and biotechnology , antigen presentation , antigen , immune system , ceramide , antigen presenting cell , biology , dendritic cell , apoptosis , t cell , cell , immunology , biochemistry , microrna , gene
Summary Defects in rapid clearance of apoptotic cells lead to an accumulation of dead cells (late apoptotic or secondary necrotic cells), which results in an aberrant immune response. However, little is known about whether and how macrophages (M φ s) cooperate with dendritic cells ( DC s) in the presentation of dead‐cell‐associated antigens in this process. By transferring high numbers of dead cells to mimic a failure of apoptotic cell clearance in vivo , we found that M φ s and neutrophils were the predominant phagocytes in the uptake of dead cells in the spleen. Moreover, both M φ s and DC s were required for an optimal CD 4 + T‐cell response triggered by dead‐cell‐associated antigens. Importantly, although M φ s alone had a poor capacity for antigen presentation, they could transfer phagocytosed antigens to DC s for potent antigen presentation to enhance T‐cell responses. Finally, we found that exosomes released from M φ s acted as a transmitter to convey antigens to DC s partially in a ceramide‐dependent manner, since treatment with the neutral sphingomyelinase inhibitor GW 4869 and spiroepoxide resulted in a significant reduction of T‐cell proliferation in vitro and in vivo . These findings point to a novel pathway of cross‐talk between M φ s and DC s, which will be helpful to explain possible mechanisms for autoimmune diseases characterized by increased rates of apoptosis.