Consequences of Cell Death

By B. Sauter, Matthew L. Albert, Loise M. Francisco, M. Larsson, Selin Somersan, N. Bhardwaj. Journal of Experimental Medicine, 2000

1,513 citations recorded by the source corpus.

Cell death by necrosis is typically associated with inflammation, in contrast to apoptosis. We have identified additional distinctions between the two types of death that occur at the level of dendritic cells (DCs) and which influence the induction of immunity. DCs must undergo changes termed maturation to act as potent antigen-presenting cells. Here, we investigated whether exposure to apoptotic or necrotic cells affected DC maturation. We found that immature DCs efficiently phagocytose a variety of apoptotic and necrotic tumor cells. However, only exposure to the latter induces maturation. The mature DCs express high levels of the DC-restricted markers CD83 and lysosome-associated membrane glycoprotein (DC-LAMP) and the costimulatory molecules CD40 and CD86. Furthermore, they develop into powerful stimulators of both CD4+ and CD8+ T cells. Cross-presentation of antigens to CD8+ T cells occurs after uptake of apoptotic cells. We demonstrate here that optimal cross-presentation of antigens from tumor cells requires two steps: phagocytosis of apoptotic cells by immature DCs, which provides antigenic peptides for major histocompatibility complex class I and class II presentation, and a maturation signal that is delivered by exposure to necrotic tumor cells, their supernatants, or standard maturation stimuli, e.g., monocyte-conditioned medium. Thus, DCs are able to distinguish two types of tumor cell death, with necrosis providing a control that is critical for the initiation of immunity.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/5db594e93af0c2c851d841c5334c8dc7e2bebca5

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Citations in the corpus

• Engulfment of apoptotic cells: signals for a good meal (2007, background): “However, a puzzling issue is that although PtdSer is also exposed on necrotic cells and can be detected with annexin-V (a molecule that binds to exposed PtdSer), the immune response that is induced by phagocytes following the engulfment of necrotic cells is pro-inflammator”
• Natural killer cells and dendritic cells: rendezvous in abused tissues (2002, background): “NK-cell-dependent DC maturation might be induced by the exposure of iDCs to necrotic materia”
• Asthma: an epidemic of dysregulated immunity (2002, background): “These T R -like cells develop in the absence of costimulation and, therefore, may be related to anergic cell”
• Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-kappa B pathway. (2000, background): “Necrotic but not apoptotic lysates deliver a maturation signal and cause translocation of NF-κB In view of the data shown in Fig. 5, and in view of the recent demonstration by Gallucci et al. (14) and Sauter et al. ( 15 ) that necrotic but not apoptotic cells mediate maturation of DC, we tested whet”
• Necroptosis: the release of damage-associated molecular patterns and its physiological relevance. (2013, background): “They include, in the case of accidental necrosis, HMGB1, IL-1a, uric acid, DNA fragments, mitochondrial content, and ATP (Tables 1 and 2) (Eigenbrod et al., 2008; Kono et al., 2010; Krysko et al., 2008a; Sauter et al., 2000).”
• Regulatory T cells in the control of immune pathology (2001, background): “; here they can efficiently phagocytose proteins and apoptotic debris arising from normal cell turnover in the tissue without becoming activate”
• Immunobiology of the TAM receptors (2008, background): “At the same time, apoptotic cells are known to have multiple immunomodulatory — but generally immunosuppressive — effects on APC”
• Necrosis, a well-orchestrated form of cell demise: signalling cascades, important mediators and concomitant immune response. (2006, background): “Immature dendritic cells efficiently phagocytose a variety of apoptotic and necrotic tumour cells, but only the latter induce maturation and optimal presentation of tumour antigens [195,196].”
• Necrotic death as a cell fate. (2006, background): “Other immunostimulatory molecules that are released by necrotic cells include adenine phosphate (Srinivas et al. 2002; Rich et al. 2003), uric acid (Shi et al. 2003), and heat-shock proteins (Sauter et al. 2000; Berwin et al. 2001; Somersan et al. 2001).”