a lysm and sh3-domain containing region of the listeria monocytogenes p60 protein stimulates accessory cells to promote activation of host nk cells单核细胞增多性李斯特氏菌的lysm和sh3-domain包含地区p60蛋白质刺激促进辅助细胞激活宿主nk细胞.pdfVIP

A LysM and SH3-Domain Containing Region of the Listeria monocytogenes p60 Protein Stimulates Accessory Cells to Promote Activation of Host NK Cells Rebecca L. Schmidt, Holly C. Filak, Jack D. Lemon, Terry A. Potter, Laurel L. Lenz* Integrated Department of Immunology, National Jewish Health and University of Colorado School of Medicine, Denver, Colorado, United States of America Abstract Listeria monocytogenes (Lm) infection induces rapid and robust activation of host natural killer (NK) cells. Here we define a region of the abundantly secreted Lm endopeptidase, p60, that potently but indirectly stimulates NK cell activation in vitro ¨ and in vivo. Lm expression of p60 resulted in increased IFNc production by naıve NK cells co-cultured with treated dendritic cells (DCs). Moreover, recombinant p60 protein stimulated activation of naive NK cells when co-cultured with TLR or cytokine primed DCs in the absence of Lm. Intact p60 protein weakly digested bacterial peptidoglycan (PGN), but neither muropeptide recognition by RIP2 nor the catalytic activity of p60 was required for NK cell activation. Rather, the immune stimulating activity mapped to an N-terminal region of p60, termed L1S. Treatment of DCs with a recombinant L1S ¨ polypeptide stimulated them to activate naıve NK cells in a cell culture model. Further, L1S treatment activated NK cells in vivo and increased host resistance to infection with Francisella tularensis live vaccine strain (LVS). These studies demonstrate an immune stimulating function for a bacterial LysM domain-containing polypeptide and suggest that recombinant versions of L1S or other p60 derivatives can be used to promote NK cell activat