A bacterial effector protein promotes nuclear translocation of Stat3 to induce IL-10.

The multifunctional Yersinia effector YopM inhibits effector triggered immunity and increases production of the anti-inflammatory cytokine Interleukin-10 (IL-10) to suppress the host immune response. Previously it was shown that YopM induces IL-10 gene expression by elevating phosphorylation of the serine-threonine kinase RSK1 in the nucleus of human macrophages. Using transcriptomics, we found that YopM strongly affects expression of genes belonging to the JAK-STAT signaling pathway.

Yersinia remodels epigenetic histone modifications in human macrophages.

Various pathogens systematically reprogram gene expression in macrophages, but the underlying mechanisms are largely unknown. We investigated whether the enteropathogen Yersinia enterocolitica alters chromatin states to reprogram gene expression in primary human macrophages. Genome-wide chromatin immunoprecipitation (ChIP) seq analyses showed that pathogen-associated molecular patterns (PAMPs) induced up- or down-regulation of histone modifications (HMod) at approximately 14500 loci in promoters and enhancers.

Activation of the macroautophagy pathway by Yersinia enterocolitica promotes intracellular multiplication and egress of yersiniae from epithelial cells.

The virulence strategy of pathogenic Yersinia spp. involves cell-invasive as well as phagocytosis-preventing tactics to enable efficient colonisation of the host organism. Enteropathogenic yersiniae display an invasive phenotype in early infection stages, which facilitates penetration of the intestinal mucosa.

Serine 25 phosphorylation inhibits RIPK1 kinase-dependent cell death in models of infection and inflammation.

RIPK1 regulates cell death and inflammation through kinase-dependent and -independent mechanisms. As a scaffold, RIPK1 inhibits caspase-8-dependent apoptosis and RIPK3/MLKL-dependent necroptosis. As a kinase, RIPK1 paradoxically induces these cell death modalities.

To die or not to die: Regulatory feedback phosphorylation circuits determine receptor-interacting protein kinase-1 (RIPK1) function.

Complex posttranslational modifications determine the effects of receptor-interacting protein kinase-1 (RIPK1) on cell survival and death. Studies from us and others have revealed a p38/MK2-dependent checkpoint in RIPK1 signaling. MAPKAP kinase 2 (MK2) phosphorylates RIPK1 to suppress RIPK1-mediated apoptosis and necroptosis in response to diverse stimuli relevant to inflammation, infection, genotoxic stress and chemotherapy.

p38/MK2-dependent phosphorylation controls cytotoxic RIPK1 signalling in inflammation and infection.

Receptor-interacting protein kinase-1 (RIPK1), a master regulator of cell fate decisions, was identified as a direct substrate of MAPKAP kinase-2 (MK2) by phosphoproteomic screens using LPS-treated macrophages and stress-stimulated embryonic fibroblasts. p38/MK2 interact with RIPK1 in a cytoplasmic complex and MK2 phosphorylates mouse RIPK1 at Ser321/336 in response to pro-inflammatory stimuli, such as TNF and LPS, and infection with the pathogen Yersinia enterocolitica. MK2 phosphorylation inhibits RIPK1 autophosphorylation, curtails RIPK1 integration into cytoplasmic cytotoxic complexes, and suppresses RIPK1-dependent apoptosis and necroptosis.

Immunosuppressive Yersinia Effector YopM Binds DEAD Box Helicase DDX3 to Control Ribosomal S6 Kinase in the Nucleus of Host Cells.

Yersinia outer protein M (YopM) is a crucial immunosuppressive effector of the plaque agent Yersinia pestis and other pathogenic Yersinia species. YopM enters the nucleus of host cells but neither the mechanisms governing its nucleocytoplasmic shuttling nor its intranuclear activities are known. Here we identify the DEAD-box helicase 3 (DDX3) as a novel interaction partner of Y.

Cell death triggered by Yersinia enterocolitica identifies processing of the proinflammatory signal adapter MyD88 as a general event in the execution of apoptosis.

Many pathogenic microorganisms have evolved tactics to modulate host cell death or survival pathways for establishing infection. The enteropathogenic bacterium Yersinia enterocolitica deactivates TLR-induced signaling pathways, which triggers apoptosis in macrophages. In this article, we show that Yersinia-induced apoptosis of human macrophages involves caspase-dependent cleavage of the TLR adapter protein MyD88.

Cytotoxic necrotizing factor-Y boosts Yersinia effector translocation by activating Rac protein.

Pathogenic Yersinia spp. translocate the effectors YopT, YopE, and YopO/YpkA into target cells to inactivate Rho family GTP-binding proteins and block immune responses. Some Yersinia spp.

Guidelines for the use and interpretation of assays for monitoring autophagy.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding.

The preferences for everyday living inventory: scale development and description of psychosocial preferences responses in community-dwelling elders.

Purpose Of The Study: Assessing preferences for daily life is the foundation for person-centered care delivery. This study tested a new measure, the Preferences for Everyday Living Inventory (PELI), with a large sample of community-dwelling older adults. We sought to evaluate the tool's convergent and divergent validity, identify the most commonly held preferences within the sample, and explore relationships between gender and race and strength of preferences.

Staphylococcus epidermidis uses distinct mechanisms of biofilm formation to interfere with phagocytosis and activation of mouse macrophage-like cells 774A.1.

Assembly of adherent biofilms is the key mechanism involved in Staphylococcus epidermidis virulence during device-associated infections. Aside from polysaccharide intercellular adhesin (PIA), the accumulation-associated protein Aap and the extracellular matrix binding protein Embp act as intercellular adhesins, mediating S. epidermidis cell aggregation and biofilm accumulation.

Activity modulation of the bacterial Rho GAP YopE: an inspiration for the investigation of mammalian Rho GAPs.

The Yersinia enterocolitica Rho GTPase Activating Protein (Rho GAP) YopE belongs to a group of bacterial virulence factors that is translocated into infected target cells by a type three secretion system. Structurally and biochemically YopE resembles eukaryotic Rho GAPs which control various cellular functions by modulating the activity of Rho GTP binding proteins. Here we summarise the published information on cellular effects, Rho protein substrates, compartmentalisation and turnover of YopE.

Destabilization of YopE by the ubiquitin-proteasome pathway fine-tunes Yop delivery into host cells and facilitates systemic spread of Yersinia enterocolitica in host lymphoid tissue.

Pathogenic Yersinia species inject a panel of Yop virulence proteins by type III protein secretion into host cells to modulate cellular defense responses. This enables the survival and dissemination of the bacteria in the host lymphoid tissue. We have previously shown that YopE of the Y.

Yersinia virulence factor YopM induces sustained RSK activation by interfering with dephosphorylation.

Background: Pathogenic yersiniae inject several effector proteins (Yops) into host cells, which subverts immune functions and enables the bacteria to survive within the host organism. YopM, whose deletion in enteropathogenic yersiniae results in a dramatic loss of virulence, has previously been shown to form a complex with and activate the multifunctional kinases PKN2 and RSK1 in transfected cells.

Methodology/principal Findings: In a near physiological approach with double-affinity-tagged YopM being translocated into the macrophage cell line J774A.

Beta1 integrin-dependent engulfment of Yersinia enterocolitica by macrophages is coupled to the activation of autophagy and suppressed by type III protein secretion.

Autophagy is a central lysosomal degradation process that is essential for the maintenance of cellular homeostasis. Autophagy has furthermore emerged as integral part of the host immune response. Autophagic processes promote the separation and degradation of intracellular microorganisms which contributes to the development of innate and adaptive immunity.

Yersinia enterocolitica differentially modulates RhoG activity in host cells.

Pathogenic bacteria of the genus Yersinia (Y. pestis, Y. enterocolitica and Y.

Crosstalk of signalling processes of innate immunity with Yersinia Yop effector functions.

The interaction of microbial pathogens with host cells critically determines the genesis of infectious diseases. Gram-negative, pathogenic bacteria from the genus Yersinia deliver a set of virulence proteins, the so-called Yersinia outer proteins (Yops), inside the eukaryotic cell where the Yops perturb key cellular functions of innate immunity. In our past work, we used Yersinia enterocolitica as a tool to explore the crosstalk between the bacterial pathogen and its host cell.

Effector functions of pathogenic Yersinia species.

Pathogenic species of the genus Yersinia suppress and reorient the immune system to infect lymphatic tissues, inner organs and at times also the vasculature. For this purpose yersiniae employ a type III secretion system to translocate effector proteins (Yersinia outer proteins; Yops) into immune cells. Yops often exert unique biochemical activities for modulating the activity of Rho GTP-binding proteins, focal adhesion proteins, inflammatory pathways and cell survival/apoptosis.

Catalytically active Yersinia outer protein P induces cleavage of RIP and caspase-8 at the level of the DISC independently of death receptors in dendritic cells.

Yersinia outer protein P (YopP) is injected by Y. enterocolitica into host cells thereby inducing apoptotic and necrosis-like cell death in dendritic cells (DC). Here we show the pathways involved in DC death caused by the catalytic activity of YopP.

Serogroup-related escape of Yersinia enterocolitica YopE from degradation by the ubiquitin-proteasome pathway.

Pathogenic Yersinia spp. employ a type III protein secretion system that translocates several Yersinia outer proteins (Yops) into the host cell to modify the host immune response. One strategy of the infected host cell to resist the bacterial attack is degradation and inactivation of injected bacterial virulence proteins through the ubiquitin-proteasome pathway.

Symptoms, affects, and self-rated health: evidence for a subjective trajectory of health.

Objective: Self-rated health (SRH) is known to predict mortality and other health outcomes better than objective ratings, suggesting that patients have important knowledge that physicians do not. The study assessed whether SRH reflects changes in internal states, specifically symptoms and affects.

Method: In an event-sampling study, 54 elders completed a SRH measure, positive and negative affect scale, a symptom checklist, and a pain scale every evening for 8 weeks.

Yersinia enterocolitica YopP inhibits MAP kinase-mediated antigen uptake in dendritic cells.

Yersinia enterocolitica (Ye) targets mouse dendritic cells (DCs) and inhibits their ability to trigger T cell activation. Here we have investigated whether Ye might interfere with antigen presentation in DCs. Infection of DCs with the Ye wild-type strain reduced OVA uptake by DCs as demonstrated by flow cytometry and confocal laser scan microscopy.