Corrigendum: Inflammatory response against via intracellular sensing of nucleic acids in keratinocytes.

[This corrects the article DOI: 10.3389/fimmu.2022.

Cefiderocol Protects against Cytokine- and Endotoxin-Induced Disruption of Vascular Endothelial Cell Integrity in an In Vitro Experimental Model.

The severe course of bloodstream infections with Gram-negative bacilli can lead to organ dysfunctions and compromise the integrity of the vascular barrier, which are the hallmarks of sepsis. This study aimed to investigate the potential effect of cefiderocol on the barrier function of vascular endothelial cells (vECs) in an in vitro experimental set-up. Human umbilical vein cells (HUVECs), co-cultured with erythrocyte-depleted whole blood for up to 48 h, were activated with tumor necrosis factor-alpha (TNF-α) or lipopolysaccharide (LPS) to induce endothelial damage in the absence or presence of cefiderocol (concentrations of 10, 40 and 70 mg/L).

Inflammatory Response Against Intracellular Sensing of Nucleic Acids in Keratinocytes.

is one of the clinically most relevant pathogens causing infections. Humans are often exposed to . In approximately one-third of the healthy population it can be found on the skin either for long or short periods as colonizing "commensals", without inducing infections or an inflammatory immune response.

Invasiveness of Is Associated with an IncFII Plasmid.

is one of the most prevalent pathogens, causing a variety of infections including bloodstream infections. At the same time, it can be found as a commensal, being part of the intestinal microflora. While it is widely accepted that pathogenic strains can evolve from colonizing strains, the evolutionary route facilitating the commensal-to-pathogen transition is complex and remains not fully understood.

Notch Ligand Delta-Like 1 Is Associated With Loss of Vascular Endothelial Barrier Function.

Vascular leakage associated with vascular endothelial cell (vEC) dysfunction is a hallmark of sepsis. Causative for the decreased integrity of the vascular endothelium (vE) is a complex concurrence of pathogen components, inflammation-associated host factors, and the interaction of vECs and activated circulating immune cells. One signaling pathway that regulates the integrity of the vE is the Notch cascade, which is activated through the binding of a Notch ligand to its respective Notch receptor.

Association Between Soluble Notch Ligand Delta-like Ligand 1 and Bleeding Complications in Patients With Dengue Fever Infection.

Bleeding associated with endothelial damage is a key feature of severe dengue fever. In the current study, we investigated whether Notch ligands were associated with bleeding in 115 patients with confirmed dengue infection in Vietnam. Soluble Notch ligands were determined by means of enzyme-linked immunosorbent assay.

Pitfalls in genotypic antimicrobial susceptibility testing caused by low expression of blaKPC in Escherichia coli.

Background: There is a growing interest in the rapid genotypic identification of antimicrobial resistance (AMR). In routine diagnostics, we detected multiple KPC-positive Escherichia coli (KPC-Ec) with discordant phenotypic meropenem susceptibility from a single patient's blood cultures, which prompted a more thorough investigation.

Objectives: We investigated the potential clinical relevance of, and the mechanism behind, discordant phenotypic and genotypic meropenem susceptibility in KPC-Ec.

Delta-like Canonical Notch Ligand 1 in Patients Following Liver Transplantation-A Secondary Analysis of a Prospective Cohort Study.

Opportunistic bacterial infections are dreaded risks in patients following liver transplantation (LTX), even though patients receive an antibiotic prophylaxis. The timely recognition of such an infection may be delayed, as culture-based diagnostic methods are linked with a relevant gap in performance. We measured plasma concentrations of Delta-like canonical Notch ligand 1 (DLL1) in 93 adult patients at seven consecutive time points after liver transplantation and correlated the results to the occurrence of culture-proven bacterial infection or a complicated clinical course (composite endpoint of two or more complications: graft rejection or failure, acute kidney failure, acute lung injury, or 90-day mortality).

Streptococcal Pyrogenic Exotoxin A-Stimulated Monocytes Mediate Regulatory T-Cell Accumulation through PD-L1 and Kynurenine.

Bacterial superantigens (SAgs) are exotoxins that promote a fulminant activation of the immune system. The subsequent intense release of inflammatory cytokines often results in hypotension, shock, and organ failure with high mortality rates. In the current paradigm, the direct and simultaneous binding of SAgs with T-cell receptor (TCR)-bearing Vβ regions and conserved structures on major histocompatibility complex class II (MHC class II) on antigen-presenting cells (APCs) induces the activation of both cell types.

Host-Derived as a Novel Diagnostic Biomarker for Bacterial Sepsis-Results From a Combinational Secondary Analysis.

Sepsis is a life-threatening syndrome, resulting from a dysbalanced host response to infection. However, especially the early, pro-inflammatory immune response in sepsis is similar to other inflammatory conditions without infectious cause, e.g.

Silencing SOCS1 via Liposome-Packed siRNA Sustains TLR4-Ligand Adjuvant.

Infectious diseases remain one of the leading causes of death worldwide. Vaccination is a powerful instrument to avert a variety of those by inducing a pathogen-specific immune response and ensure a long-lasting protection against the respective infection. Nevertheless, due to increasing numbers of immunocompromised patients and emergence of more aggressive pathogens existing vaccination techniques are limited.

The Interplay of Notch Signaling and STAT3 in TLR-Activated Human Primary Monocytes.

The highly conserved Notch signaling pathway essentially participates in immunity through regulation of developmental processes and immune cell activity. In the adaptive immune system, the impact of the Notch cascade in T and B differentiation is well studied. In contrast, the function, and regulation of Notch signaling in the myeloid lineage during infection is poorly understood.

Hsa-miR-99b/let-7e/miR-125a Cluster Regulates Pathogen Recognition Receptor-Stimulated Suppressive Antigen-Presenting Cells.

Antigen-presenting cells (APCs) regulate the balance of our immune response toward microbes. Whereas immunogenic APCs boost inflammation and activate lymphocytes, the highly plastic cells can switch into a tolerogenic/suppressive phenotype that dampens and resolves the response. Thereby the initially mediated inflammation seems to prime the switch of APCs while the strength of activation determines the grade of the suppressive phenotype.

IL-1β As Mediator of Resolution That Reprograms Human Peripheral Monocytes toward a Suppressive Phenotype.

During infection pathogen-associated molecular patterns activate immune cells to initiate a cascade of reactions leading to inflammation and the activation of the adaptive immune response culminating in the elimination of foreign pathogens. However, shortly after activation of the host defense machinery, a return to homeostasis is preferred to prevent inflammation-induced tissue damage. This switch from the initial immunogenic to the subsequent tolerogenic phase after clearance of the infection can be mediated through highly plastic peripheral monocytes.

Analysis of the interplay between all-trans retinoic acid and histone deacetylase inhibitors in leukemic cells.

The treatment of acute promyelocytic leukemia (APL) with all-trans retinoic acid (ATRA) induces granulocytic differentiation. This process renders APL cells resistant to cytotoxic chemotherapies. Epigenetic regulators of the histone deacetylases (HDACs) family, which comprise four classes (I-IV), critically control the development and progression of APL.

Phospho-Flow Analysis of Primary Mouse Cells After HDAC Inhibitor Treatment.

Flow cytometric techniques allow fast, sensitive, and multiparametric analyses at the single cell level. This makes it possible to distinguish subsets of cells within heterogeneous samples. Moreover, flow cytometry has become a frequently used method for the evaluation of therapeutic effects.

Pasteurella multocida Toxin Manipulates T Cell Differentiation.

Pasteurella multocida causes various diseases in a broad range of wild and domestic animals. Toxigenic strains of the serotypes A and D produce an AB protein toxin named Pasteurella multocida toxin (PMT). PMT constitutively activates the heterotrimeric G protein subunits Gαq, Gα13, and Gαi through deamidation of a glutamine residue, which results in cytoskeletal rearrangements as well as increased proliferation and survival of the host cell.

T-cell activation or tolerization: the Yin and Yang of bacterial superantigens.

Bacterial superantigens (SAg) are exotoxins from pathogens which interact with innate and adaptive immune cells. The paradox that SAgs cause activation and inactivation/anergy of T-cells was soon recognized. The structural and molecular events following SAg binding to antigen presenting cells (APCs) followed by crosslinking of T-cell receptors were characterized in detail.

Erythropoietin acts as an anti-inflammatory signal on murine mast cells.

Recently it was found that the erythropoietin receptor (EpoR) is expressed on innate immune cells, such as dendritic cells and macrophages. We found that murine bone marrow-derived mast cells express the EpoR and that its expression is increased under hypoxic conditions. Interestingly, Epo stimulation of the cells did not activate signal transducer and activator of transcription molecules, nor did we find differences in the expression of typical STAT-dependent genes, the proliferation rate, and the ability to differentiate or to protect the cells from apoptosis.

Granzyme A produces bioactive IL-1β through a nonapoptotic inflammasome-independent pathway.

Bacterial components are recognized by the immune system through activation of the inflammasome, eventually causing processing of the proinflammatory cytokine interleukin-1? (IL-1?), a pleiotropic cytokine and one of the most important mediators of inflammation, through the protease caspase-1. Synthesis of the precursor protein and processing into its bioactive form are tightly regulated, given that disturbed control of IL-1? release can cause severe autoinflammatory diseases or contribute to cancer development. We show that the bacterial Pasteurella multocida toxin (PMT) triggers Il1b gene transcription in macrophages independently of Toll-like receptor signaling through RhoA/Rho-kinase-mediated NF-?? activation.

Signaling cascades of Pasteurella multocida toxin in immune evasion.

Pasteurella multocida toxin (PMT) is a protein toxin found in toxigenic strains of Pasteurella multocida. PMT is the causative agent for atrophic rhinitis in pigs, a disease characterized by loss of nasal turbinate bones due to an inhibition of osteoblast function and an increase in osteoclast activity and numbers. Apart from this, PMT acts as a strong mitogen, protects from apoptosis and has an impact on the differentiation and function of immune cells.

Regulation of Toll-like receptor 4-mediated immune responses through Pasteurella multocida toxin-induced G protein signalling.

Background: Lipopolysaccharide (LPS)-triggered Toll-like receptor (TLR) 4-signalling belongs to the key innate defence mechanisms upon infection with Gram-negative bacteria and triggers the subsequent activation of adaptive immunity. There is an active crosstalk between TLR4-mediated and other signalling cascades to secure an effective immune response, but also to prevent excessive inflammation. Many pathogens induce signalling cascades via secreted factors that interfere with TLR signalling to modify and presumably escape the host response.

Histone deacetylase inhibitors block IFNγ-induced STAT1 phosphorylation.

Signal transducer and activator of transcription 1 (STAT1) is important for innate and adaptive immunity. Histone deacetylase inhibitors (HDACi) antagonize unbalanced immune functions causing chronic inflammation and cancer. Phosphorylation and acetylation regulate STAT1 and different IFNs induce phosphorylated STAT1 homo-/heterodimers, e.