Dendritic cell function is perturbed by Yersinia enterocolitica infection in vitro.
Infection with Yersinia enterocolitica is the cause of intestinal or extraintestinal diseases. We investigated the role of dendritic cells (DC), the most potent antigen-presenting cell (APC), in the course of infection with Y. enterocolitica in vitro. For these studies, DC were isolated from human peripheral blood and infected with green fluorescent protein (GFP)-labelled Y. enterocolitica. Bacteria were found within DC by FACS analysis and viable bacteria could be cultured from lysed cells. Within 24 h after infection, DC upregulated CD83 and CD86 followed at day 3, indicating maturation of DC. In contrast, for MHC class II, a marked but transient downregulation was observed at day 3 after infection, and downregulation to a lesser extent for CD80 at day 5. To assess the immunostimulatory capacity of DC, viable infected and uninfected DC were incubated with autologous T cells in the presence of phytohemagglutinin A (PHA). T cell proliferation was significantly reduced at days 4-6 after infection but not thereafter, whereas nonpathogenic Escherichia coli was not able to mimick this suppressive effect of Y. enterocolitica. The same suppression could be observed when infected DC were used in a mixed leucocyte reaction with allogeneic T cells. Thus Y. enterocolitica is able to invade DC, does not induce necrosis or apoptosis, but affects maturation of DC. However, MHC class II-molecules are downregulated initially, which coincides with a diminished immunostimulatory capacity of DC infected with Y. enterocolitica. The diminished immunostimulatory capacity of DC following infection with Y. enterocolitica in vitro might impair or delay elimination of bacteria thereby contributing to pathogenesis of bacterial enteritis or extraintestinal manifestations such as reactive arthritis.
Schoppet
M
M
Children's Hospital, University of Würzburg, and Lehrstuhl für Mikrobiologie, Theodor-Boveri-Institut für Biowissenschaften, Universität Würzburg, Würzburg, Germany.
Bubert
A
A
Huppertz
H I
HI
D015703:Antigens, CD / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D015415:Biomarkers; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D015008:Yersinia enterocolitica / Q000276:immunology*; D000097802:CD83 Antigen
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D015415:Biomarkers; D000949:Histocompatibility Antigens Class II; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D010835:Phytohemagglutinins; D000097802:CD83 Antigen; C497964:CD86 protein, human