Mycoplasmal Lipoproteins Induce Toll-Like Receptor 2- and Caspases-Mediated Cell Death in Lymphocytes and Monocytes

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Abstract
Lipoproteins of Mycoplasma salivarium and Mycoplasma fermentans preferentially induced necrotic cell death in lymphocytic cell lines, MOLT‐4 and Raji, and in one monocytic cell line, THP‐1, whereas they preferentially induced apoptotic cell death in another monocytic cell line, HL‐60. These findings were also supported by ultrastructural observations by the use of scanning and transmission electron microscopes and by agarose gel electrophoresis of the genomic DNA. The lipoproteins activated caspase‐3 in both MOLT‐4 and HL‐60 cells, which was assessed by the cleavage of the synthetic substrate DEVD‐pNA and the endogenous substrate poly(ADP‐ribose) polymerase. The cytotoxicity to MOLT‐4 and HL‐60 cells was inhibited by various caspase inhibitors, Ac‐DMQD‐CHO, Ac‐IETD‐CHO, and Z‐VAD‐FMK. The cytotoxicity was also partially suppressed by the monoclonal antibody to Toll‐like receptor 2. Thus this study demonstrated that mycoplasmal lipoproteins induce caspases‐dependent necrotic and apoptotic cell death in lymphocytes and monocytes/macrophages, which is partially induced by TLR2‐mediated signaling.