Calciphylaxis in a Middle-Aged Asian Patient: An Unusual Cause of Disc Swelling.

Calciphylaxis resulting in ischemic optic neuropathy secondary to calcification of the central retinal artery is a rare occurrence. Only 12 reports of calciphylaxis resulting in optic neuropathy have been published. While it is important to consider giant cell arteritis (GCA) in cases of acute vision loss with pallid disc swelling, clinicians must also maintain a high index of suspicion of calciphylaxis in a patient with risk factors of hypercalcaemia.

Polyamines: Key Players in Immunometabolism and Immune Regulation.

Polyamines are small organic molecules ubiquitously present in all living organisms and function as crucial regulators of biological processes ranging from fundamental cellular metabolism to immune regulation. Dysregulation of polyamine metabolism has been implicated in numerous diseases, including neurodegenerative disorders, inflammatory conditions, autoimmune diseases, and cancer. This review provides an overview of pathophysiology of these conditions, highlighting polyamines' role in immunometabolic alterations in the context of immune regulation.

Neuroimmune cell interactions and chronic infections in oral cancers.

Inflammation is a process that is associated with the activation of distal immunosuppressive pathways that have evolved to restore homeostasis and prevent excessive tissue destruction. However, long-term immunosuppression resulting from systemic and local inflammation that may stem from dysbiosis, infections, or aging poses a higher risk for cancers. Cancer incidence and progression dramatically increase with chronic infections including HIV infection.

Beta-defensin index: A functional biomarker for oral cancer detection.

There is an unmet clinical need for a non-invasive and cost-effective test for oral squamous cell carcinoma (OSCC) that informs clinicians when a biopsy is warranted. Human beta-defensin 3 (hBD-3), an epithelial cell-derived anti-microbial peptide, is pro-tumorigenic and overexpressed in early-stage OSCC compared to hBD-2. We validate this expression dichotomy in carcinoma in situ and OSCC lesions using immunofluorescence microscopy and flow cytometry.

Distinct SARS-CoV-2 specific NLRP3 and IL-1β responses in T cells of aging patients during acute COVID-19 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19) that presents with varied clinical manifestations ranging from asymptomatic or mild infections and pneumonia to severe cases associated with cytokine storm, acute respiratory distress syndrome (ARDS), and even death. The underlying mechanisms contributing to these differences are unclear, although exacerbated inflammatory sequelae resulting from infection have been implicated. While advanced aging is a known risk factor, the precise immune parameters that determine the outcome of SARS-CoV-2 infection in elderly individuals are not understood.

Polyamine metabolism impacts T cell dysfunction in the oral mucosa of people living with HIV.

Metabolic changes in immune cells contribute to both physiological and pathophysiological outcomes of immune reactions. Here, by comparing protein expression, transcriptome, and salivary metabolome profiles of uninfected and HIV+ individuals, we found perturbations of polyamine metabolism in the oral mucosa of HIV+ patients. Mechanistic studies using an in vitro human tonsil organoid infection model revealed that HIV infection of T cells also resulted in increased polyamine synthesis, which was dependent on the activities of caspase-1, IL-1β, and ornithine decarboxylase-1.

Inflammation, Immune Senescence, and Dysregulated Immune Regulation in the Elderly.

An optimal immune response requires the appropriate interaction between the innate and the adaptive arms of the immune system as well as a proper balance of activation and regulation. After decades of life, the aging immune system is continuously exposed to immune stressors and inflammatory assaults that lead to immune senescence. In this review, we will discuss inflammaging in the elderly, specifically concentrating on IL-6 and IL-1b in the context of T lymphocytes, and how inflammation is related to mortality and morbidities, specifically cardiovascular disease and cancer.

Fungal Colonization and Infections-Interactions with Other Human Diseases.

is a commensal fungus that asymptomatically colonizes the skin and mucosa of 60% of healthy individuals. Breaches in the cutaneous and mucosal barriers trigger candidiasis that ranges from asymptomatic candidemia and mucosal infections to fulminant sepsis with 70% mortality rates. Fungi influence at least several diseases, in part by mechanisms such as the production of pro-carcinogenic agents, molecular mimicking, and triggering of the inflammation cascade.

Regulation of IL-17A-Producing Cells in Skin Inflammatory Disorders.

This review focuses on the IL-17A family of cytokines produced by T lymphocytes and other immune cells and how they are involved in cutaneous pathogenic responses. It will also discuss cutaneous dysbiosis and FOXP3 regulatory T cells in the context of inflammatory conditions linked to IL-17 responses in the skin. Specifically, it will review key literature on chronic mucocutaneous candidiasis and psoriasis.

Oral immune dysfunction is associated with the expansion of FOXP3PD-1Amphiregulin T cells during HIV infection.

Residual systemic inflammation and mucosal immune dysfunction persist in people living with HIV, despite treatment with combined anti-retroviral therapy, but the underlying immune mechanisms are poorly understood. Here we report that the altered immune landscape of the oral mucosa of HIV-positive patients on therapy involves increased TLR and inflammasome signaling, localized CD4 T cell hyperactivation, and, counterintuitively, enrichment of FOXP3 T cells. HIV infection of oral tonsil cultures in vitro causes an increase in FOXP3 T cells expressing PD-1, IFN-γ, Amphiregulin and IL-10.

The Role of Dectin-1 Signaling in Altering Tumor Immune Microenvironment in the Context of Aging.

An increased accumulation of immune-dysfunction-associated CD4Foxp3 regulatory T cells (T) is observed in aging oral mucosa during infection. Here we studied the function of T during oral cancer development in aging mucosa. First, we found heightened proportions of T and myeloid-derived suppressor cells (MDSC) accumulating in mouse and human oral squamous cell carcinoma (OSCC) tissues.

Naïve CD4+ T Cell Lymphopenia and Apoptosis in Chronic Hepatitis C Virus Infection Is Driven by the CD31+ Subset and Is Partially Normalized in Direct-Acting Antiviral Treated Persons.

Background: The mechanisms underlying naïve CD4+ lymphopenia during chronic Hepatitis C Virus (HCV) infection are unclear. Whether direct-acting antiviral (DAA) therapy restores peripheral naïve CD4+ T cell numbers and function is unknown.

Methods: We enumerated frequencies and counts of peripheral naïve CD4+, CD4+CD31+ and CD4+CD31- T cells by flow cytometry in a cross sectional analysis comparing chronic HCV infected (n=34), DAA-treated(n=29), and age-range matched controls (n=25), as well as in a longitudinal cohort of HCV DAA treated persons (n=16).

IL-1β-MyD88-mTOR Axis Promotes Immune-Protective IL-17AFoxp3 Cells During Mucosal Infection and Is Dysregulated With Aging.

CD4Foxp3T maintain immune homeostasis, but distinct mechanisms underlying their functional heterogeneity during infections are driven by specific cytokine milieu. Here we show that MyD88 deletion in Foxp3 cells altered their function and resulted in increased fungal burden and immunopathology during oral (CA) challenge. Excessive inflammation due to the absence of MyD88 in T coincided with a reduction of the unique population of IL-17A expressing Foxp3 cells (T17) and an increase in dysfunctional IFN-γ/Foxp3 cells (TIFN-γ) in infected mice.

Innate immune mechanisms to oral pathogens in oral mucosa of HIV-infected individuals.

A crucial aspect of mucosal HIV transmission is the interaction between HIV, the local environmental milieu and immune cells. The oral mucosa comprises many host cell types including epithelial cells, CD4 + T cells, dendritic cells and monocytes/macrophages, as well as a diverse microbiome predominantly comprising bacterial species. While the oral epithelium is one of the first sites exposed to HIV through oral-genital contact and nursing infants, it is largely thought to be resistant to HIV transmission via mechanisms that are still unclear.

Microbiome Dependent Regulation of T and Th17 Cells in Mucosa.

Mammals co-exist with resident microbial ecosystem that is composed of an incredible number and diversity of bacteria, viruses and fungi. Owing to direct contact between resident microbes and mucosal surfaces, both parties are in continuous and complex interactions resulting in important functional consequences. These interactions govern immune homeostasis, host response to infection, vaccination and cancer, as well as predisposition to metabolic, inflammatory and neurological disorders.

A Pilot Study Identifying Brain-Targeting Adaptive Immunity in Pediatric Extracorporeal Membrane Oxygenation Patients With Acquired Brain Injury.

Objectives: Extracorporeal membrane oxygenation provides short-term cardiopulmonary life support, but is associated with peripheral innate inflammation, disruptions in cerebral autoregulation, and acquired brain injury. We tested the hypothesis that extracorporeal membrane oxygenation also induces CNS-directed adaptive immune responses which may exacerbate extracorporeal membrane oxygenation-associated brain injury.

Design: A single center prospective observational study.

Tau Is Elevated in Pediatric Patients on Extracorporeal Membrane Oxygenation.

Neurologic injury is a known and feared complication of extracorporeal membrane oxygenation (ECMO). Neurologic biomarkers may have a role in assisting in early identification of such. Axonal biomarker tau has not been investigated in the pediatric ECMO population.

Cycling CD4+ T cells in HIV-infected immune nonresponders have mitochondrial dysfunction.

Immune nonresponder (INR) HIV-1-infected subjects are characterized by their inability to reconstitute the CD4+ T cell pool after antiretroviral therapy. This is linked to poor clinical outcome. Mechanisms underlying immune reconstitution failure are poorly understood, although, counterintuitively, INRs often have increased frequencies of circulating CD4+ T cells in the cell cycle.

Role of Short Chain Fatty Acids in Controlling T and Immunopathology During Mucosal Infection.

Interactions between mucosal tissues and commensal microbes control appropriate host immune responses and inflammation, but very little is known about these interactions. Here we show that the depletion of resident bacteria using antibiotics (Abx) causes oral and gut immunopathology during oropharyngeal candidiasis (OPC) infection. Antibiotic treatment causes reduction in the frequency of Foxp3+ regulatory cells (T) and IL-17A producers, with a concomitant increase in oral tissue pathology.

Identification of Casz1 as a Regulatory Protein Controlling T Helper Cell Differentiation, Inflammation, and Immunity.

While T helper (Th) cells play a crucial role in host defense, an imbalance in Th effector subsets due to dysregulation in their differentiation and expansion contribute to inflammatory disorders. Here, we show that Casz1, whose function is previously unknown in CD4 T cells, coordinates Th differentiation and . Casz1 deficiency in CD4 T cells lowers susceptibility to experimental autoimmune encephalomyelitis, consistent with the reduced frequency of Th17 cells, despite an increase in Th1 cells in mice.

Kaposi's sarcoma-associated herpesvirus infection promotes differentiation and polarization of monocytes into tumor-associated macrophages.

Tumor associated macrophages (TAMs) promote angiogenesis, tumor invasion and metastasis, and suppression of anti-tumor immunity. These myeloid cells originate from monocytes, which differentiate into TAMs upon exposure to the local tumor microenvironment. We previously reported that Kaposi's sarcoma-associated herpes virus (KSHV) infection of endothelial cells induces the cytokine angiopoietin-2 (Ang-2) to promote migration of monocytes into tumors.