Crosstalk between Signaling Processes of Innate Immunity and Yersinia YopP Effector Functions

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Enteropathogenic Yersinia species have evolved multiple strategies to interfere with the immune response of the host, which enables extracellular multiplication of the bacteria in the host lymphoid tissue. One outstanding feature of immune modulation by Yersinia is the induction of apoptosis in macrophages. Yersinia engages a type III protein secretion system to translocate a number of virulence factors, the so-called Yops, inside the host cell cytoplasm. One of these Yops, YopP, targets the NF-kB-activating kinase IKKb, which inhibits activation of transcription factor NF-kB and suppresses NF-kB-dependent antiapoptotic activities. The simultaneous initiation of proapoptotic signaling by Yersinia infection or LPS treatment results in macrophage apoptosis. Thus, Yersinia exploits the mechanisms of innate immunity to mediate macrophage cell death. In the current project, we want to characterize the impact of signaling processes of innate immunity on Yersinia-induced effector functions. Initially, we want to elucidate by which mechanisms Yersinia activates signaling pathways of innate immunity. The cytotoxic signals of innate immunity and their contribution to Yersinia-induced apoptosis will be determined. Finally, we want to characterize the pathogenetic significance of these findings in vivo in the Yersinia-mouse infection model. Together, this data should reveal new aspects of the mechanisms of microbe-host cell interaction and provide new insights into signaling of innate immunity.