Regulation of Paneth cell-specific genes in COVID-19 patients and SARS-CoV-2-infected mice by quantification of mRNA from exfoliated cells in stool samples.

The Paneth cell, a secretory cell of the small intestine, expresses numerous host defense proteins, and is hypothesized to play an important role in host defense against infection. However, studying gene expression in this cell requires invasive procedures. To test the hypothesis that we could observe Paneth cell-specific gene regulation from exfoliated cells in infectious conditions, we obtained stool samples from patients with COVID-19 and uninfected controls.

An enhanced IL17 and muted type I interferon nasal epithelial cell state characterizes severe COVID-19 with fungal coinfection.

Unlabelled: Recent case reports and epidemiological data suggest that fungal infections represent an underappreciated complication among people with severe COVID-19. However, the frequency of fungal colonization in patients with COVID-19 and associations with specific immune responses in the airways remain incompletely defined. We previously generated a single-cell RNA-sequencing data set characterizing the upper respiratory microenvironment during COVID-19 and mapped the relationship between disease severity and the local behavior of nasal epithelial cells and infiltrating immune cells.

A focused retrospective study on differences in IBD characteristics between Black and White patients in the south.

Background: Most facets of Inflammatory Bowel Disease (IBD) have not been thoroughly compared among minority populations, including Black patients. Our study was designed to characterize the demographics, phenotypes, outcomes, healthcare utilization, and treatment of IBD in a large cohort with 38% Black patients.

Methods: Electronic health records of 3272 IBD patients seen in a tertiary academic medical network from 2012 to July 15th, 2019 were analyzed.

Black Inflammatory Bowel Disease Patients Have Lower Response to Antitumor Necrosis Factor Agents Compared With White Patients.

Background: Most studies on the safety and efficacy of antitumor necrosis factor alpha (anti-TNF) agents in the treatment of inflammatory bowel disease have included few Black patients.

Aims: We aimed to evaluate the therapeutic response rate in Black IBD patients compared with White patients.

Methods: We conducted a retrospective review of IBD patients who were treated with anti-TNF agents and assessed those with therapeutic drug levels for clinical, endoscopic, and radiologic response to anti-TNF treatment.

COVID-19 Plasma Extracellular Vesicles Increase the Density of Lipid Rafts in Human Small Airway Epithelial Cells.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is the causative agent of the COVID-19 disease. COVID-19 viral infection can affect many cell types, including epithelial cells of the lungs and airways. Extracellular vesicles (EVs) are released by virtually all cell types, and their packaged cargo allows for intercellular communication, cell differentiation, and signal transduction.

Severe COVID-19 is associated with fungal colonization of the nasopharynx and potent induction of IL-17 responses in the nasal epithelium.

Recent case reports and epidemiological data suggest fungal infections represent an under-appreciated complication among people with severe COVID-19. However, the frequency of fungal colonization in patients with COVID-19 and associations with specific immune responses in the airways remain incompletely defined. We previously generated a single-cell RNA-sequencing (scRNA-seq) dataset characterizing the upper respiratory microenvironment during COVID-19, and mapped the relationship between disease severity and the local behavior of nasal epithelial cells and infiltrating immune cells.

NKTR-255 is a polymer-conjugated IL-15 with unique mechanisms of action on T and natural killer cells.

NKTR-255 is a PEG conjugate of recombinant human IL-15 (rhIL-15) being examined as a potential cancer immunotherapeutic. Since IL-15 responses can be mediated by trans or cis presentation via IL-15Rα or soluble IL-15/IL-15Rα complexes, we investigated the role of IL-15Rα in driving NKTR-255 responses using defined naive and memory OVA-specific CD8+ T cells (OT-I) and NK cells in mice. NKTR-255 induced a 2.

Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19.

SARS-CoV-2 infection can cause severe respiratory COVID-19. However, many individuals present with isolated upper respiratory symptoms, suggesting potential to constrain viral pathology to the nasopharynx. Which cells SARS-CoV-2 primarily targets and how infection influences the respiratory epithelium remains incompletely understood.

The gut microbiome of COVID-19 recovered patients returns to uninfected status in a minority-dominated United States cohort.

To investigate the relationship between intestinal microbiota and SARS-CoV-2-mediated pathogenicity in a United States, majority African American cohort. We prospectively collected fecal samples from 50 SARS-CoV-2 infected patients, 9 SARS-CoV-2 recovered patients, and 34 uninfected subjects seen by the hospital with unrelated respiratory medical conditions (controls). 16S rRNA sequencing and qPCR analysis was performed on fecal DNA/RNA.

Small intestinal immunopathology and GI-associated antibody formation in hereditary alpha-tryptasemia.

Background: Hereditary alpha-tryptasemia (HαT) is characterized by elevated basal serum tryptase due to increased copies of the TPSAB1 gene. Individuals with HαT frequently present with multisystem complaints, including anaphylaxis and seemingly functional gastrointestinal (GI) symptoms.

Objective: We sought to determine the prevalence of HαT in an irritable bowel syndrome cohort and associated immunologic characteristics that may distinguish patients with HαT from patients without HαT.

Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19.

Infection with SARS-CoV-2, the virus that causes COVID-19, can lead to severe lower respiratory illness including pneumonia and acute respiratory distress syndrome, which can result in profound morbidity and mortality. However, many infected individuals are either asymptomatic or have isolated upper respiratory symptoms, which suggests that the upper airways represent the initial site of viral infection, and that some individuals are able to largely constrain viral pathology to the nasal and oropharyngeal tissues. Which cell types in the human nasopharynx are the primary targets of SARS-CoV-2 infection, and how infection influences the cellular organization of the respiratory epithelium remains incompletely understood.

Regulatory CD4 T cells inhibit HIV-1 expression of other CD4 T cell subsets via interactions with cell surface regulatory proteins.

During chronic HIV-1 infection, regulatory CD4 T cells (Tregs) frequently represent the largest subpopulation of CD4 T cell subsets, implying relative resistant to HIV-1. When HIV-1 infection of CD4 T cells was explored in vitro and ex vivo from patient samples, Tregs possessed lower levels of HIV-1 DNA and RNA in comparison with conventional effector and memory CD4 T cells. Moreover, Tregs suppressed HIV-1 expression in other CD4 T cells in an in vitro co-culture system.

The potential and promise of IL-15 in immuno-oncogenic therapies.

This review provides an in-depth description of the preclinical and clinical studies demonstrating the effectiveness and limitations of IL-15 and IL-15 analogs given as an exogenous immuno-oncology agent. IL-15 is a cytokine that primarily stimulates the proliferation and cytotoxic functions of CD8T cells and NK cells leading to enhanced anti-tumor responses. While initially showing promise as a cancer therapeutic, the efficacy of IL-15 was limited by its short in vivo half-life.

Characterization of Human Blood Monocytes and Intestinal Macrophages.

Monocytes and macrophages play fundamental roles in defense against microbes, clearance of senescent and dead cells, and immunoregulation. Although blood monocytes are the source of intestinal macrophages in the developed mucosal immune system, blood monocytes and intestinal macrophages from healthy human subjects display distinct phenotypic and functional differences. Blood monocytes can be induced to polarize into M1 and M2 macrophages, whereas intestinal macrophages appear to be terminally differentiated and are unable to undergo such inducible polarization.

CD4 regulatory T cells augment HIV-1 expression of polarized M1 and M2 monocyte derived macrophages.

Previous in vitro studies have shown that the HIV-1 virus can alter the cytokine/chemokine profile of polarized macrophages which may lead to their increased susceptibility to viral infection. Here, we found that M2 monocyte derived macrophages (MDM) were significantly more permissive to productive infection by R5-tropic HIV-1 strains, including transmitted founder (T/F) viruses, than M1 MDM. Previous in vitro studies by our lab showed that regulatory T cells (Tregs) suppress HIV-1 infection in non-Treg CD4 T cells.