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Kirschnek, S.* ; Scheffel, J.* ; Heinzmann, U. ; Häcker, G.*

Necrosis-like cell death induced by bacteria in mouse macrophages.

Eur. J. Immunol. 34, 1461-1471 (2004)

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The death of individual cells is a frequent and physiological event in the mammalian immune system and most often occurs by apoptosis. It is becoming increasingly clear that cell death is alsoinduced during bacterial infections. Here we report that, in addition to the apoptotic form already established, a necrosis-like form of cell death is induced by pyogenic bacteria (Enterobacteriaceae, Pseudomonas, enterococci) in mouse macrophages. Necrosis could be separated from apoptosis as it did not require phagocytosis of bacteria and occurred when apoptosis was inhibited by caspase blockade or by Bcl-2. Furthermore, ligands that stimulate Toll-like receptors were also found to have the capacity to induce necrosis. Strikingly, this form of cell death was sufficient for the uptake of dead cells by either mouse bone marrow-derived DC or a cell line derived from DC, possibly by virtue of the externalization of phosphatidylserine. Since the loading with bacteria-carrying cells is likely to impact on DC function, this form of necrosis may have a previously unsuspected role in the development of an immune response.

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