Yersinia outer protein P inhibits CD8 T cell priming in the mouse infection model.
Pathogenic yersiniae translocate a mixture of effector proteins called Yersinia outer proteins (Yops) into the cytosol of eukaryotic cells by their type III secretion system. YopP is one of the best characterized of these effector proteins and known to inhibit the proinflammatory response of the host by interfering with NF-kappaB signal transduction and inducing apoptosis of macrophages. The effects of YopP on the immune response were studied by a Yersinia Ag-independent approach using bacteria that translocate the well-characterized model Ag listeriolysin O of Listeria monocytogenes via their type III secretion system. In this study we demonstrate a novel function for YopP in vivo. It is shown for the first time that YopP not only counteracts the innate immune defense but also inhibits the adaptive immune system by suppressing the development of an effective CD8 T cell response in a mouse model. A possible mechanism for this could be the inhibition of Ag presentation by dendritic cells (DC). In vitro this is shown to be due to the rapid induction of programmed DC death and to inhibition of DC maturation. Using this approach we could further show that the listeriolysin O-specific CD8 T cells generated in vivo by the yopP mutant are functional and are able to protect mice against a lethal challenge with wild type Listeria.
Trülzsch
Konrad
K
Max von Pettenkofer Institut für Hygiene und Medizinische Mikrobiologie, Ludwig Maximilians Universität, München, Germany. truelzsch@m3401.mpk.med.uni-muenchen.de <truelzsch@m3401.mpk.med.uni-muenchen.de>
Geginat
Gernot
G
Sporleder
Thorsten
T
Ruckdeschel
Klaus
K
Hoffmann
Reinhardt
R
Heesemann
Jürgen
J
Rüssmann
Holger
H
D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000276:immunology / Q000502:physiology*; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology; D001854:Bone Marrow Cells; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology*; D004195:Disease Models, Animal; D006360:Heat-Shock Proteins / Q000235:genetics / Q000276:immunology; D006460:Hemolysin Proteins; D007111:Immunity, Cellular; D007113:Immunity, Innate; D008087:Listeria / Q000737:chemistry; D051379:Mice; D015009:Yersinia Infections / Q000276:immunology*; D015008:Yersinia enterocolitica / Q000737:chemistry* / Q000276:immunology
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; C109227:YopP protein, Yersinia; C038705:hlyA protein, Listeria monocytogenes