Perforin pores in the endosomal membrane trigger the release of endocytosed granzyme B into the cytosol of target cells.
Jerome Thiery,Dennis Keefe,Dennis Keefe,Steeve Boulant,Steeve Boulant,Emmanuel Boucrot,Emmanuel Boucrot,Michael Walch,Michael Walch,Denis Martinvalet,Denis Martinvalet,Denis Martinvalet,Ing Swie Goping,R. Chris Bleackley,Tomas Kirchhausen,Tomas Kirchhausen,Judy Lieberman,Judy Lieberman +17 more
TLDR
It is shown that perforin formed pores in the gigantosome membrane, allowing endosomal cargo, including granzymes, to be gradually released.Abstract:
How the pore-forming protein perforin delivers apoptosis-inducing granzymes to the cytosol of target cells is uncertain. Perforin induces a transient Ca2+ flux in the target cell, which triggers a process to repair the damaged cell membrane. As a consequence, both perforin and granzymes are endocytosed into enlarged endosomes called 'gigantosomes'. Here we show that perforin formed pores in the gigantosome membrane, allowing endosomal cargo, including granzymes, to be gradually released. After about 15 min, gigantosomes ruptured, releasing their remaining content. Thus, perforin delivers granzymes by a two-step process that involves first transient pores in the cell membrane that trigger the endocytosis of granzyme and perforin and then pore formation in endosomes to trigger cytosolic release.read more
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Interleukin-15-induced CD56(+) myeloid dendritic cells combine potent tumor antigen presentation with direct tumoricidal potential
Sébastien Anguille,Eva Lion,Jurjen Tel,I. Jolanda M. de Vries,Karen Couderé,Phillip D. Fromm,Viggo Van Tendeloo,Evelien Smits,Zwi N. Berneman +8 more
TL;DR: It is shown that IL-15 DCs, in addition to potent tumor antigen-presenting function, possess tumoricidal potential and thus qualify for the designation of killer DCs and lends further support to their implementation in DC-based immunotherapy protocols.
Journal ArticleDOI
Structure-function relationships of nonviral gene vectors: Lessons from antimicrobial polymers.
Haonan Xing,Mei Lu,Tianzhi Yang,Hui Liu,Yanping Sun,Xiaoyun Zhao,Hui Xu,Li Yang,Pingtian Ding +8 more
TL;DR: The structure-function relationships of antimicrobial polymers and gene vectors are summarized, with which the design of more advanced nonviral gene vectors is anticipated to be further boosted in the future.
Book ChapterDOI
Perforin: A Key Pore-Forming Protein for Immune Control of Viruses and Cancer
Jerome Thiery,Judy Lieberman +1 more
TL;DR: This chapter describes the current understanding of how PFN accomplishes its rate-limiting function, where PFN is expressed and how its expression is regulated, the biogenesis and storage of PFN in killer cells and how they are protected from potential damage.
Journal ArticleDOI
Molecular characterization of HCMV-specific immune responses: Parallels between CD8(+) T cells, CD4(+) T cells, and NK cells
Felipe A. Vieira Braga,Kirsten M. L. Hertoghs,René A. W. van Lier,Klaas P. J. M. van Gisbergen +3 more
TL;DR: It is proposed that the overlap in differentiation of NK cells, CD4+ and CD8+ T cells after HCMV infection may be regulated by a shared transcriptional machinery.
Journal ArticleDOI
Antigen-specific CD8 + T cell feedback activates NLRP3 inflammasome in antigen-presenting cells through perforin
Yikun Yao,Siyuan Chen,Mengtao Cao,Xing Fan,Tao Yang,Y Huang,Xinyang Song,Yongqin Li,Lilin Ye,Nan Shen,Yufang Shi,Xiaoxia Li,Feng Wang,Youcun Qian +13 more
TL;DR: It is shown that CD8+ T-cell feedback activates the NLRP3 inflammasome in APCs in an antigen-dependent manner to promote IL-1β maturation and contributes to the induction of antigen-specific antitumour immunity and pathogenesis of graft-versus-host diseases.
References
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Perforin Gene Defects in Familial Hemophagocytic Lymphohistiocytosis
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