Interaction ofYersinia pestiswith Macrophages: Limitations in YopJ-Dependent Apoptosis

Abstract

The enteropathogenicYersiniastrains are known to downregulate signaling pathways in macrophages by effectors of the type III secretion system, in which YopJ/YopP plays a crucial role. The adverse effects ofYersinia pestis, the causative agent of plague, were examined by infecting J774A.1 cells, RAW264.7 cells, and primary murine macrophages with the EV76 strain and with the fully virulent Kimberley53 strain.Y. pestisexerts YopJ-dependent suppression of tumor necrosis factor alpha secretion and phosphorylation of mitogen-activated protein kinases and thus resembles enteropathogenicYersinia. However,Y. pestisis less able to activate caspases, to suppress NF-κB activation, and to induce apoptosis in macrophages than the high-virulenceY. enterocoliticaWA O:8 strain. These differences appear to be related to lower efficiency of YopJ effector translocation byY. pestis. The efficiencies of effector translocation and of apoptosis induction can be enhanced either by using a high bacterial load in a synchronized infection or by overexpressing exogenous YopJ inY. pestis. Replacing YopJ with the homologousY. enterocoliticaeffector YopP can further enhance these effects. Overexpression of YopP in ayopJ-deletedY. pestisbackground leads to rapid and effective translocation into target cells, providingY. pestiswith the high cytotoxic potential ofY. enterocoliticaWA O:8. We suggest that the relative inferiority ofY. pestisin triggering cell death in macrophages may be advantageous for its in vivo propagation in the early stages of infection.