Overcoming immunosuppression in cancer: how ketogenic diets boost immune checkpoint blockade.

Immune checkpoint blockade (ICB) is now part of the standard of care in the treatment of many forms of cancer, yet it lacks efficacy in some patients, necessitating adjunct therapies to support the anti-tumor immune response. Ketogenic diets (KDs), i.e.

Meningitis and intracranial abscess due to Mycoplasma pneumoniae in a B cell-depleted patient with multiple sclerosis.

Mycoplasma pneumoniae, a frequent respiratory pathogen, can cause neurological disease manifestations. We here present a case of M. pneumoniae as cause of meningitis and occurrence of an intracranial abscess as a complication of mastoiditis with septic cerebral venous sinus thrombosis in a patient with multiple sclerosis on anti-CD20 therapy.

Prediction of Clinically Significant Prostate Cancer Using Multiparametric MRI, Biparametric MRI, and Clinical Parameters.

Introduction: Multiparametric MRI (mpMRI) is gold standard for the primary diagnostic work-up of clinically significant prostate cancer (csPCa). The aim of this study was to assess the benefit of the perfusion sequence and the non-inferiority of an MRI without contrast administration (bpMRI) compared to mpMRI while taking clinical parameters into account.

Methods: In this retrospective, non-interventional study we examined MRI data from 355 biopsy-naïve patients, performed on a 3T MRI system, evaluated by a board-certified radiologist with over 10 years of experience with subsequent mpMRI-TRUS fusion biopsy.

Divergent effects of itaconate isomers on growth in macrophages and in axenic culture.

Aconitate decarboxylase-1 (ACOD1) is expressed by activated macrophages and generates itaconate that exerts anti-microbial and immunoregulatory effects. ACOD1-itaconate is essential for macrophage-mediated control of the intracellular pathogen , which causes Q fever. Two isomers of itaconate, mesaconate and citraconate, have overlapping yet distinct activity on macrophage metabolism and inflammatory gene expression.

Gut Pathobiont-Derived Outer Membrane Vesicles Drive Liver Inflammation and Fibrosis in Primary Sclerosing Cholangitis-Associated Inflammatory Bowel Disease.

Background & Aims: Primary sclerosing cholangitis (PSC), often associated with inflammatory bowel disease (IBD), presents a multifactorial etiology involving genetic, immunologic, and environmental factors. Gut dysbiosis and bacterial translocation have been implicated in PSC-IBD, yet the precise mechanisms underlying their pathogenesis remain elusive. Here, we describe the role of gut pathobionts in promoting liver inflammation and fibrosis due to the release of bacterial outer membrane vesicles (OMVs).

Comparison of the transcriptome, lipidome, and c-di-GMP production between BCGΔBCG1419c and BCG, with Mincle- and Myd88-dependent induction of proinflammatory cytokines in murine macrophages.

We have previously reported the transcriptomic and lipidomic profile of the first-generation, hygromycin-resistant (Hyg) version of the BCGΔBCG1419c vaccine candidate, under biofilm conditions. We recently constructed and characterized the efficacy, safety, whole genome sequence, and proteomic profile of a second-generation version of BCGΔBCG1419c, a strain lacking the BCG1419c gene and devoid of antibiotic markers. Here, we compared the antibiotic-less BCGΔBCG1419c with BCG.

Multiplex Assays in Allergy Diagnosis: Allergy Explorer 2 versus ImmunoCAP ISAC E112i.

ImmunoCAP ISAC E112i (ISAC) and Allergy Explorer 2 (ALEX) detect specific immunoglobulin E (IgE) reactivity. Both multiplex assays contain molecular allergens and ALEX additionally includes allergen extracts and inhibitors that block the binding of IgE to cross-reacting carbohydrate determinants (CCDs). This study aimed to compare the performance of ISAC and ALEX by determining the IgE reactivity against allergen extracts and/or allergen components and by using qualitative, semiquantitative, and quantitative analyses of all comparable allergen components in sera from 216 participants recruited in South Tyrol/Italy.

Adjuvant PD-1 Checkpoint Inhibition in Early Cutaneous Melanoma: Immunological Mode of Action and the Role of Ultraviolet Radiation.

Melanoma ranks as the fifth most common solid cancer in adults worldwide and is responsible for a significant proportion of skin-tumor-related deaths. The advent of immune checkpoint inhibition with anti-programmed death protein-1 (PD-1) antibodies has revolutionized the adjuvant treatment of high-risk, completely resected stage III/IV melanoma. However, not all patients benefit equally.

Control of immune cell signaling by the immuno-metabolite itaconate.

Immune cell activation triggers signaling cascades leading to transcriptional reprogramming, but also strongly impacts on the cell's metabolic activity to provide energy and biomolecules for inflammatory and proliferative responses. Macrophages activated by microbial pathogen-associated molecular patterns and cytokines upregulate expression of the enzyme ACOD1 that generates the immune-metabolite itaconate by decarboxylation of the TCA cycle metabolite cis-aconitate. Itaconate has anti-microbial as well as immunomodulatory activities, which makes it attractive as endogenous effector metabolite fighting infection and restraining inflammation.

Can Perfusion-Based Brain Tissue Oxygenation MRI Support the Understanding of Cerebral Abscesses In Vivo?

Purpose: The clinical condition of a brain abscess is a potentially life-threatening disease. The combination of MRI-based imaging, surgical therapy and microbiological analysis is critical for the treatment and convalescence of the individual patient. The aim of this study was to evaluate brain tissue oxygenation measured with dynamic susceptibility contrast perfusion weighted imaging (DSC-PWI) in patients with brain abscess and its potential benefit for a better understanding of the environment in and around brain abscesses.

Intestinal helminth co-infection and associated factors among pulmonary tuberculosis patients in Africa and Asia: a systematic review and meta-analysis.

Introduction: Tuberculosis (TB) and intestinal helminths have huge public health importance, and they are geographically overlapped. Data about the burden of intestinal helminth and TB co-infection in these areas are fragmented. In this systematic review and meta-analysis we compile the current literatures and generate pooled prevalence.

TNF promotes DECTIN2 family C-type lectin receptor expression in human macrophages.

TNF blockade constitutes an effective therapy for inflammatory bowel disease, yet increases the risk for infection, including active tuberculosis. The DECTIN2 family C-type lectin receptors MINCLE, MCL, and DECTIN2 sense mycobacterial ligands and activate myeloid cells. In mice, upregulation of DECTIN2 family C-type lectin receptor after stimulation with Mycobacterium bovis Bacille Calmette-Guérin requires TNF.

Topical Diacerein Decreases Skin and Splenic CD11c Dendritic Cells in Psoriasis.

Psoriasis is an inflammatory skin disease characterized by increased neo-vascularization, keratinocyte hyperproliferation, a pro-inflammatory cytokine milieu and immune cell infiltration. Diacerein is an anti-inflammatory drug, modulating immune cell functions, including expression and production of cytokines, in different inflammatory conditions. Therefore, we hypothesized that topical diacerein has beneficial effects on the course of psoriasis.

Revisiting the Role of the CXCL13/CXCR5-Associated Immune Axis in Melanoma: Potential Implications for Anti-PD-1-Related Biomarker Research.

CXCL13 is a potent chemoattractant cytokine that promotes the migration of cells expressing its cognate receptor, CXCR5. Accordingly, T follicular helper cells and B cells migrate towards B cell follicles in lymph nodes, where the resulting spatial proximity promotes B cell/T cell interaction and antibody formation. Moreover, effector cells of the CXCL13/CXCR5-associated immune axis express PD-1, with corresponding circulating cells occurring in the blood.

IL-4 and helminth infection downregulate MINCLE-dependent macrophage response to mycobacteria and Th17 adjuvanticity.

The myeloid C-type lectin receptor (CLR) MINCLE senses the mycobacterial cell wall component trehalose-6,6'-dimycolate (TDM). Recently, we found that IL-4 downregulates MINCLE expression in macrophages. IL-4 is a hallmark cytokine in helminth infections, which appear to increase the risk for mycobacterial infection and active tuberculosis.

Different phenotypes of drug-induced anaphylaxis-Data from the European Anaphylaxis Registry.

Background: Drugs are a frequent cause of severe anaphylactic reactions. Here, we analyze a large dataset on drug induced anaphylaxis regarding elicitors, risk factors, symptoms, and treatment.

Methods: Data from the European Anaphylaxis Registry (2007-2019) with 1815 reported cases of drug-induced anaphylaxis were studied accordingly.

Macrophages inhibit Coxiella burnetii by the ACOD1-itaconate pathway for containment of Q fever.

Infection with the intracellular bacterium Coxiella (C.) burnetii can cause chronic Q fever with severe complications and limited treatment options. Here, we identify the enzyme cis-aconitate decarboxylase 1 (ACOD1 or IRG1) and its product itaconate as protective host immune pathway in Q fever.

C/EBPβ regulates lipid metabolism and isoform 2 expression in alveolar macrophages.

Pulmonary alveolar proteinosis (PAP) is a syndrome characterized by accumulation of surfactant lipoproteins within the lung alveoli. Alveolar macrophages (AMs) are crucial for surfactant clearance, and their differentiation depends on colony-stimulating factor 2 (CSF2), which regulates the establishment of an AM-characteristic gene regulatory network. Here, we report that the transcription factor CCAAT/enhancer binding protein β (C/EBPβ) is essential for the development of the AM identity, as demonstrated by transcriptome and chromatin accessibility analysis.

Ketogenic diets slow melanoma growth in vivo regardless of tumor genetics and metabolic plasticity.

Background: Growing evidence supports the use of low-carbohydrate/high-fat ketogenic diets as an adjunctive cancer therapy. However, it is unclear which genetic, metabolic, or immunological factors contribute to the beneficial effect of ketogenic diets. Therefore, we investigated the effect of ketogenic diets on the progression and metabolism of genetically and metabolically heterogeneous melanoma xenografts, as well as on the development of melanoma metastases in mice with a functional immune system.

Phosphatidylinositol 3-Kinase (PI3K) Orchestrates Aspergillus fumigatus-Induced Eosinophil Activation Independently of Canonical Toll-Like Receptor (TLR)/C-Type-Lectin Receptor (CLR) Signaling.

Eosinophilia is associated with various persisting inflammatory diseases and often coincides with chronic fungal infections or fungal allergy as in the case of allergic bronchopulmonary aspergillosis (ABPA). Here, we show that intranasal administration of live Aspergillus fumigatus conidia causes fatal lung damage in eosinophilic interleukin-5 (IL-5)-transgenic mice. To further investigate the activation of eosinophils by A.

Monocytes Elicit a Neutrophil-Independent Th1/Th17 Response Upon Immunization With a Mincle-Dependent Glycolipid Adjuvant.

Successful subunit vaccination with recombinant proteins requires adjuvants. The glycolipid trehalose-dibehenate (TDB), a synthetic analog of the mycobacterial cord factor, potently induces Th1 and Th17 immune responses and is a candidate adjuvant for human immunization. TDB binds to the C-type lectin receptor Mincle and triggers Syk-Card9-dependent APC activation.