Suppression of innate immune signaling by Yersinia YopJ

Univ Of Massachusetts Med Sch Worcester, Worcester MA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Yersinia pestis and related pathogens secrete virulence effector proteins (Yops) into mammalian cells during infection. These proteins inhibit phagocytosis and innate immune signal transduction, disabling the host response to infection. The function of several Yops has been characterized, however YopJ remains a mystery. Though it is known to interfere with the important nuclear factor kappa-B (NF-kB) and mitogen-activated protein kinase signaling pathways, the target(s) and mechanism of this activity are unknown. One potential function of YopJ is to disrupt innate immunity by the blocking the signaling pathways initiated by Toll-like receptors (TLRs), which detect conserved pathogen-derived molecules. The purpose of this study is to elucidate the pathway and protein targets of YopJ and its effect on TLR-mediated signaling. This proposal will also address the biochemical mechanism by which YopJ disables the host response. Increased understanding of YopJ function may provide a therapeutic target for the treatment of plague, a major focus of the current biodefense initiative. In addition, the NF-kB-suppressing capability of YopJ makes it a possible treatment for sepsis and/or cancer. [unreadable] [unreadable]