title: Modulation of dendritic cell differentiation and function by YopJ of Yersinia pestis.
abstract: Yersinia pestis evades immune responses in part by injecting into host immune cells several effector proteins called Yersinia outer proteins (Yops) that impair cellular function. This has been best characterized in the innate effector cells, but much less so for cells involved in adaptive immune responses. Dendritic cells (DC) sit at the crossroads between innate and adaptive immunity, and can function to initiate or inhibit adaptive immune responses. Although Y. pestis can target and inactivate DC, the mechanism responsible for this remains unclear. We have found that injection of Y. pestis YopJ into DC progenitors disrupts key signal transduction pathways and interferes with DC differentiation and subsequent function. YopJ injection prevents up-regulation of the NF-kappaB transcription factor Rel B and inhibits MAPK/ERK activation--both having key roles in DC differentiation. Furthermore, YopJ injection prevents costimulatory ligand up-regulation, LPS-induced cytokine expression, and yields differentiated DC with diminished capability to induce T cell proliferation and IFN-gamma induction. By modulating DC function through YopJ-mediated disruption of signaling pathways during progenitor to DC differentiation, Yersinia may interfere with the adaptive responses necessary to clear the infection as well as establish a tolerant immune environment that leads to chronic infection/carrier state in the surviving host.
authors: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, USA.
authors: Inna
authors: I
authors: Lindner
authors: Julie
authors: J
authors: Torruellas-Garcia
authors: Julie
authors: J
authors: Torrvellas-Garcia
authors: Despina
authors: D
authors: Kolonias
authors: Louise M
authors: LM
authors: Carlson
authors: Khaled A
authors: KA
authors: Tolba
authors: Gregory V
authors: GV
authors: Plano
authors: Kelvin P
authors: KP
authors: Lee
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D015010:Yersinia pestis / Q000145:classification / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D008024:Ligands; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; C109227:YopP protein, Yersinia