Yersinia enterocolitica Induces Apoptosis and Inhibits Surface Molecule Expression and Cytokine Production in Murine Dendritic Cells

ABSTRACT Yersinia enterocolitica evades innate immunity by expression of a variety of pathogenicity factors. Therefore, adaptive immunity including CD4+ T cells plays an important role in defense against Y. enterocolitica. We investigated whether Y. enterocolitica might target dendritic cells (DC) involved in adaptive T-cell responses. For this purpose, murine DC were infected with Y. enterocolitica wild-type and mutant strains prior to incubation with ovalbumin (OVA) as antigen and 5-(6)-carboxyfluorescein diacetate N-succinimidyl ester-labeled OVA-specific T cells from DO11.10 mice. While T-cell proliferation was partially affected by infection of DC with plasmid-cured and YopP-deficient Yersinia mutant strains, no T-cell proliferation occurred after infection of DC with wild-type Y. enterocolitica. Infection of DC with Y. enterocolitica wild type resulted in decreased up-regulation of major histocompatibility complex class II, CD54 (intercellular adhesion molecule 1), CD 80, and CD86 expression. Experiments with plasmid-cured Y. enterocolitica or a YopP-deficient mutant strain revealed that YopP accounts for inhibition of surface molecule expression. Wild-type Y. enterocolitica suppressed the release of KC, tumor necrosis factor alpha, interleukin-10 (IL-10), and IL-12 by DC, while infection of DC with plasmid-cured Y. enterocolitica or with the YopP-deficient mutant resulted in the production of these cytokines. Moreover, infection with wild-type Y. enterocolitica induced apoptosis in DC mediated by YopP. Apoptosis occurred despite translocation of NF-κB to the nucleus, as demonstrated by electromobility shift assays. Together, these data demonstrate that Y. enterocolitica targets functions of murine DC that are required for T-cell activation. This might contribute to evasion of adaptive immune responses by Y. enterocolitica.

[1]  S. Akira,et al.  Toll-like receptor-dependent production of IL-12p40 causes chronic enterocolitis in myeloid cell-specific Stat3-deficient mice. , 2003, The Journal of clinical investigation.

[2]  A. Yoshimura,et al.  Involvement of Suppressor of Cytokine Signaling-3 as a Mediator of the Inhibitory Effects of IL-10 on Lipopolysaccharide-Induced Macrophage Activation1 , 2002, The Journal of Immunology.

[3]  Bali Pulendran,et al.  Lipopolysaccharides from Distinct Pathogens Induce Different Classes of Immune Responses In Vivo1 , 2001, The Journal of Immunology.

[4]  P. Vandenabeele,et al.  Yersinia enterocolitica YopP-induced Apoptosis of Macrophages Involves the Apoptotic Signaling Cascade Upstream of Bid* , 2001, The Journal of Biological Chemistry.

[5]  A. Bubert,et al.  Dendritic cell function is perturbed by Yersinia enterocolitica infection in vitro , 2000, Clinical and experimental immunology.

[6]  Y. Chien,et al.  Suppression of T and B Lymphocyte Activation by a Yersinia pseudotuberculosis Virulence Factor, Yoph , 1999, The Journal of experimental medicine.

[7]  J. Dixon,et al.  Inhibition of the mitogen-activated protein kinase kinase superfamily by a Yersinia effector. , 1999, Science.

[8]  G. Schuler,et al.  An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. , 1999, Journal of immunological methods.

[9]  S. Akira,et al.  Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils. , 1999, Immunity.

[10]  W. Lee,et al.  Visualizing memory phenotype development after in vitro stimulation of CD4(+) T cells. , 1998, Cellular immunology.

[11]  M. Neurath,et al.  The yopJ locus is required for Yersinia‐mediated inhibition of NF‐κB activation and cytokine expression: YopJ contains a eukaryotic SH2‐like domain that is essential for its repressive activity , 1998, Molecular microbiology.

[12]  G. Cornelis,et al.  Role of YopP in Suppression of Tumor Necrosis Factor Alpha Release by Macrophages during YersiniaInfection , 1998, Infection and Immunity.

[13]  J. Heesemann,et al.  Yersinia enterocolitica Impairs Activation of Transcription Factor NF-κB: Involvement in the Induction of Programmed Cell Death and in the Suppression of the Macrophage Tumor Necrosis Factor α Production , 1998, The Journal of experimental medicine.

[14]  J. Bliska,et al.  YopJ of Yersinia pseudotuberculosis is required for the inhibition of macrophage TNF‐α production and downregulation of the MAP kinases p38 and JNK , 1998, Molecular microbiology.

[15]  J. Heesemann,et al.  IL-18 (IFN-gamma-inducing factor) regulates early cytokine production in, and promotes resolution of, bacterial infection in mice. , 1998, Journal of immunology.

[16]  A. Lanzavecchia,et al.  The duration of antigenic stimulation determines the fate of naive and effector T cells. , 1998, Immunity.

[17]  J. Heesemann,et al.  Interaction of Yersinia enterocolitica with macrophages leads to macrophage cell death through apoptosis , 1997, Infection and immunity.

[18]  J. Bliska,et al.  Identification of p130Cas as a substrate of Yersinia YopH (Yop51), a bacterial protein tyrosine phosphatase that translocates into mammalian cells and targets focal adhesions , 1997, The EMBO journal.

[19]  Maria Fällman,et al.  The PTPase YopH inhibits uptake of Yersinia, tyrosine phosphorylation of p130Cas and FAK, and the associated accumulation of these proteins in peripheral focal adhesions , 1997, The EMBO journal.

[20]  G. Cornelis,et al.  Differential secretion of interleukin-8 by human epithelial cell lines upon entry of virulent or nonvirulent Yersinia enterocolitica , 1996, Infection and immunity.

[21]  D. Taub,et al.  T lymphocyte recruitment by interleukin-8 (IL-8). IL-8-induced degranulation of neutrophils releases potent chemoattractants for human T lymphocytes both in vitro and in vivo. , 1996, The Journal of clinical investigation.

[22]  I. Autenrieth,et al.  IL-12 is essential for resistance against Yersinia enterocolitica by triggering IFN-gamma production in NK cells and CD4+ T cells. , 1996, Journal of immunology.

[23]  W. Kast,et al.  MHC class II compartments and the kinetics of antigen presentation in activated mouse spleen dendritic cells. , 1995, Journal of immunology.

[24]  J. Heesemann,et al.  Immune responses to Yersinia enterocolitica in susceptible BALB/c and resistant C57BL/6 mice: an essential role for gamma interferon , 1994, Infection and immunity.

[25]  A. B. Lyons,et al.  Determination of lymphocyte division by flow cytometry. , 1994, Journal of immunological methods.

[26]  P. Hantschmann,et al.  Immunohistological characterization of the cellular immune response against Yersinia enterocolitica in mice: evidence for the involvement of T lymphocytes. , 1993, Immunobiology.

[27]  I. Autenrieth,et al.  T lymphocytes mediate protection against Yersinia enterocolitica in mice: characterization of murine T-cell clones specific for Y. enterocolitica , 1992, Infection and immunity.

[28]  A. Heimberger,et al.  Induction by antigen of intrathymic apoptosis of CD4+CD8+TCRlo thymocytes in vivo. , 1990, Science.

[29]  W. Schaffner,et al.  Rapid detection of octamer binding proteins with 'mini-extracts', prepared from a small number of cells. , 1989, Nucleic acids research.

[30]  Chang-Joo,et al.  Plasmid-mediated resistance to phagocytosis in Yersinia enterocolitica , 1987, Infection and immunity.