Glutamine promotes human CD8+ T cells and counteracts imiquimod-induced T cell hyporesponsiveness.

T cells protect tissues from cancer. Although investigations in mice showed that amino acids (AA) critically regulate T cell immunity, this remains poorly understood in humans. Here, we describe the AA composition of interstitial fluids in keratinocyte-derived skin cancers (KDSCs) and study the effect of AA on T cells using models of primary human cells and tissues. Gln contributed to ∼15% of interstitial AAs and promoted interferon gamma (IFN-γ), but not granzyme B (GzB) expression, in CD8+ T cells. Furthermore, the Toll-like receptor 7 agonist imiquimod (IMQ), a common treatment for KDSCs, down-regulated the metabolic gatekeepers c-MYC and mTORC1, as well as the AA transporter ASCT2 and intracellular Gln, Asn, Ala, and Asp in T cells. Reduced proliferation and IFN-γ expression, yet increased GzB, paralleled IMQ effects on AA. Finally, Gln was sufficient to promote IFN-γ-production in IMQ-treated T cells. Our findings indicate that Gln metabolism can be harnessed for treating KDSCs.

[Bacterial infections of the skin in the context of climate change and migration]. / Bakterielle Infektionen der Haut im Kontext von Klimawandel und Migration.

BACKGROUND: In the context of climate change and migration, both common and previously less common pathogens are gaining importance as cutaneous bacterial infections. OBJECTIVE: To inform medical professionals about challenges to dermatology posed by climate change and migration. MATERIALS AND METHODS: Review of the current literature on emerging antimicrobial resistance and emerging pathogens in general and on the epidemiological situation in Germany in particular. RESULTS: Climate change has a direct impact on microbiological ecosystems in Germany's warming coastal waters leading to an increase of marine V. vulnificus counts and human infections. Secondary to global warming, transmitting vectors of, for example, Lyme disease, rickettsioses and tularemia are also increasing. In addition, infectious diseases like cutaneous diphtheria and mycobacteriosis have been diagnosed in migrants, mostly likely acquired before migration or on the migration route and first diagnosed in Germany. In this context, antimicrobial resistance (e.g. methicillin-resistant Staphylococcus aureus [MRSA] and multidrug-resistant gram-negative bacteria) is gaining importance. CONCLUSION: Due to progressive changes in global climate and ongoing migration, the aforementioned pathogens of infectious skin diseases and changes in antimicrobial resistance patterns have to be expected. Physicians should be aware of these developments in order to offer appropriate diagnostics and treatment. Epidemiological and biogeographic monitoring will be indispensable for managing emerging changes.

Macrophage Biology in Human Granulomatous Skin Inflammation.

Cutaneous granulomatoses represent a heterogeneous group of diseases, which are defined by macrophage infiltration in the skin. Skin granuloma can be formed in the context of infectious and non-infectious conditions. Recent technological advances have deepened our understanding of the pathophysiology of granulomatous skin inflammation, and they provide novel insights into human tissue macrophage biology at the site of ongoing disease. Here, we discuss findings on macrophage immune function and metabolism derived from three prototypic cutaneous granulomatoses: granuloma annulare, sarcoidosis, and leprosy.

Clinical, laboratory and radiological characteristics and outcomes of novel coronavirus (SARS-CoV-2) infection in humans: A systematic review and series of meta-analyses.

New evidence on the COVID-19 pandemic is being published daily. Ongoing high-quality assessment of this literature is therefore needed to enable clinical practice to be evidence-based. This review builds on a previous scoping review and aimed to identify associations between disease severity and various clinical, laboratory and radiological characteristics. We searched MEDLINE, CENTRAL, EMBASE, Scopus and LILACS for studies published between January 1, 2019 and March 22, 2020. Clinical studies including ≥10 patients with confirmed COVID-19 of any study design were eligible. Two investigators independently extracted data and assessed risk of bias. A quality effects model was used for the meta-analyses. Subgroup analysis and meta-regression identified sources of heterogeneity. For hospitalized patients, studies were ordered by overall disease severity of each population and this order was used as the modifier variable in meta-regression. Overall, 86 studies (n = 91,621) contributed data to the meta-analyses. Severe disease was strongly associated with fever, cough, dyspnea, pneumonia, any computed tomography findings, any ground glass opacity, lymphocytopenia, elevated C-reactive protein, elevated alanine aminotransferase, elevated aspartate aminotransferase, older age and male sex. These variables typically increased in prevalence by 30-73% from mild/early disease through to moderate/severe disease. Among hospitalized patients, 30-78% of heterogeneity was explained by severity of disease. Elevated white blood cell count was strongly associated with more severe disease among moderate/severe hospitalized patients. Elevated lymphocytes, low platelets, interleukin-6, erythrocyte sedimentation rate and D-dimers showed potential associations, while fatigue, gastrointestinal symptoms, consolidation and septal thickening showed non-linear association patterns. Headache and sore throat were associated with the presence of disease, but not with more severe disease. In COVID-19, more severe disease is strongly associated with several clinical, laboratory and radiological characteristics. Symptoms and other variables in early/mild disease appear non-specific and highly heterogeneous. Clinical Trial Registration: PROSPERO CRD42020170623.