Method to Assess Immunosenescent CD8 T Cells in Respiratory Viral Infections.

Immunosenescence is a well-characterized phenomenon that occurs with increasing age in all immune and somatic cells. In order to best study immunosenescence, it is imperative to develop methods to accurately identify immunosenescent cells. Elderly patients are known to have impaired immune responses to respiratory viruses, and it is hypothesized that this is due, in part, to immunosenescent, terminally exhausted CD8 T cells.

Cell-intrinsic regulation of phagocyte function by interferon lambda during pulmonary viral, bacterial super-infection.

Influenza infections result in a significant number of severe illnesses annually, many of which are complicated by secondary bacterial super-infection. Primary influenza infection has been shown to increase susceptibility to secondary methicillin-resistant Staphylococcus aureus (MRSA) infection by altering the host immune response, leading to significant immunopathology. Type III interferons (IFNs), or IFNλs, have gained traction as potential antiviral therapeutics due to their restriction of viral replication without damaging inflammation.

Monocyte Production of C1q Potentiates CD8 T-Cell Function Following Respiratory Viral Infection.

Respiratory viral infections remain a leading cause of morbidity and mortality. Using a murine model of human metapneumovirus, we identified recruitment of a C1q-expressing inflammatory monocyte population concomitant with viral clearance by adaptive immune cells. Genetic ablation of C1q led to reduced CD8 T-cell function.

IFN-λ drives distinct lung immune landscape changes and antiviral responses in human metapneumovirus infection.

Unlabelled: Human metapneumovirus (HMPV) is a primary cause of acute respiratory infection, yet there are no approved vaccines or antiviral therapies for HMPV. Early host responses to HMPV are poorly characterized, and further understanding could identify important antiviral pathways. Type III interferon (IFN-λ) displays potent antiviral activity against respiratory viruses and is being investigated for therapeutic use.

PD-1 signaling in neonates restrains CD8 T cell function and protects against respiratory viral immunopathology.

Respiratory viral infections, including human metapneumovirus (HMPV), remain a leading cause of morbidity and mortality in neonates and infants. However, the mechanisms behind the increased sensitivity to those respiratory viral infections in neonates are poorly understood. Neonates, unlike adults, have several anti-inflammatory mechanisms in the lung, including elevated baseline expression of programmed death ligand 1 (PD-L1), a ligand for the inhibitory receptor programmed cell death protein 1 (PD-1).

PD-1 Impairs CD8+ T Cell Granzyme B Production in Aged Mice during Acute Viral Respiratory Infection.

CD8+ T cell dysfunction contributes to severe respiratory viral infection outcomes in older adults. CD8+ T cells are the primary cell type responsible for viral clearance. With increasing age, CD8+ T cell function declines in conjunction with an accumulation of cytotoxic tissue-resident memory (TRM) CD8+ T cells.

Terminally exhausted CD8 T cells contribute to age-dependent severity of respiratory virus infection.

Background: Lower respiratory infections are a leading cause of severe morbidity and mortality among older adults. Despite ubiquitous exposure to common respiratory pathogens throughout life and near universal seropositivity, antibodies fail to effectively protect the elderly. Therefore, we hypothesized that severe respiratory illness in the elderly is due to deficient CD8 T cell responses.

Virion glycosylation influences mycobacteriophage immune recognition.

Glycosylation of eukaryotic virus particles is common and influences their uptake, trafficking, and immune recognition. In contrast, glycosylation of bacteriophage particles has not been reported; phage virions typically do not enter the cytoplasm upon infection, and they do not generally inhabit eukaryotic systems. We show here that several genomically distinct phages of Mycobacteria are modified with glycans attached to the C terminus of capsid and tail tube protein subunits.

Human Metapneumovirus Reinfection in Aged Mice Recapitulates Increased Disease Severity in Elderly Humans Infected with Human Metapneumovirus.

Human metapneumovirus (HMPV) is a leading cause of respiratory infection in adults >65 y. Nearly all children worldwide are seropositive for HMPV by age 5 y, but reinfections occur throughout life, and there is no licensed vaccine. Recurrent HMPV infection is mild and self-resolving in immunocompetent individuals.

Solution-phase synthesis of the chalcogenide perovskite barium zirconium sulfide as colloidal nanomaterials.

Chalcogenide perovskites such as BaZrS have promising optoelectronic properties. Methods to produce these materials at low temperatures, especially in the solution phase, are currently scarce. We describe a solution-phase synthesis of colloidal nanoparticles of BaZrS using reactive metal amide precursors.

Liver Microabscesses in a Premature Neonate With Eosinophilic Colitis.

Hepatic abscesses in premature infants are rare with less than 100 case reports documented in literature. We report a case of a premature infant diagnosed with hepatic microabscesses secondary to eosinophilic colitis. A 33 4/7-week preterm female neonate presented with bilious emesis, abdominal distention, and severe hematochezia.

Neonatal Immune Responses to Respiratory Viruses.

Respiratory tract infections are a leading cause of morbidity and mortality in newborns, infants, and young children. These early life infections present a formidable immunologic challenge with a number of possibly conflicting goals: simultaneously eliminate the acute pathogen, preserve the primary gas-exchange function of the lung parenchyma in a developing lung, and limit long-term sequelae of both the infection and the inflammatory response. The latter has been most well studied in the context of childhood asthma, where multiple epidemiologic studies have linked early life viral infection with subsequent bronchospasm.

IL-17RA-signaling in Lgr5 intestinal stem cells induces expression of transcription factor ATOH1 to promote secretory cell lineage commitment.

The Th17 cell-lineage-defining cytokine IL-17A contributes to host defense and inflammatory disease by coordinating multicellular immune responses. The IL-17 receptor (IL-17RA) is expressed by diverse intestinal cell types, and therapies targeting IL-17A induce adverse intestinal events, suggesting additional tissue-specific functions. Here, we used multiple conditional deletion models to identify a role for IL-17A in secretory epithelial cell differentiation in the gut.

Interleukin-22 signaling attenuates necrotizing enterocolitis by promoting epithelial cell regeneration.

Necrotizing enterocolitis (NEC) is a deadly intestinal inflammatory disorder that primarily affects premature infants and lacks adequate therapeutics. Interleukin (IL)-22 plays a critical role in gut barrier maintenance, promoting epithelial regeneration, and controlling intestinal inflammation in adult animal models. However, the importance of IL-22 signaling in neonates during NEC remains unknown.

A Review of the Immunomodulating Components of Maternal Breast Milk and Protection Against Necrotizing Enterocolitis.

Breast milk contains immunomodulating components that are beneficial to newborns during maturation of their immune system. Human breast milk composition is influenced by an infant's gestational and chronological age, lactation stage, and the mother and infant's health status. Major immunologic components in human milk, such as secretory immunoglobulin A (IgA) and growth factors, have a known role in regulating gut barrier integrity and microbial colonization, which therefore protect against the development of a life-threatening gastrointestinal illness affecting newborn infants called necrotizing enterocolitis (NEC).

Exposure to cuticular bacteria can alter host behavior in a funnel-weaving spider.

Contact with environmental microbes are arguably the most common species interaction in which any animal participates. Studies have noted diverse relationships between hosts and resident microbes, which can have strong consequences for host development, physiology, and behavior. Many of these studies focus specifically on pathogens or beneficial microbes, while the benign microbes, of which the majority of bacteria could be described, are often ignored.

Erratum: Exposure to cuticular bacteria can alter host behavior in a funnel-weaving spider.

[This corrects the article DOI: 10.1093/cz/zox064.]

Interleukin-22 Signaling in the Regulation of Intestinal Health and Disease.

Interleukin (IL)-22 is a member of the IL-10 family of cytokines that has been extensively studied since its discovery in 2000. This review article aims to describe the cellular sources and signaling pathways of this cytokine as well as the functions of IL-22 in the intestine. In addition, this article describes the roles of IL-22 in the pathogenesis of several gastrointestinal diseases, including inhibition of inflammation and barrier defense against pathogens within the intestine.

Supercritical fluid extraction of methyltestosterone, nortestosterone and testosterone at low ppb levels from fortified bovine urine.

A multi-residue supercritical fluid extraction (SFE) method is proposed for the isolation of nortestosterone, testosterone and methyltestosterone from bovine urine. Prior to SFE, bovine urine was hydrolyzed and then fortified with the three steroids at 100 ng/ml and 50 ng/ml each for HPLC analysis and 25 ng/ml and 12.5 ng/ml each for GC-MS analysis.

Determination of melengestrol acetate in supercritical fluid-solid phase extracts of bovine fat tissue by HPLC-UV and GC-MS.

A method is developed for the determination of melengestrol acetate in bovine fat tissue at or less than the established tolerance level of 25 ppb. The procedure uses a combination of supercritical fluid extraction (SFE) and solid-phase extraction (SPE) techniques to produce an extract suitable for analysis with either high-performance liquid chromatography with ultraviolet detection or gas chromatography-mass spectrometry. Overall recovery of the analyte from bovine fat tissue is 99.

Isolation of sulfonamides from fortified chicken tissues with supercritical CO2 and in-line adsorption.

Improved recoveries and detectability of three sulfonamides from chicken tissues by supercritical fluid extraction (SFE), without modifiers, using an in-line adsorption trap, are reported. Following SFE, the analytes are recovered from neutral alumina with the HPLC mobile phase. Samples are injected directly onto high-performance liquid chromatographic columns without post-extraction cleanup.

Stability of sulfaquinoxaline, sulfadimethoxine, and their N4-acetyl derivatives in chicken tissues during frozen storage.

The N4-acetyl derivatives of sulfaquinoxaline and sulfadimethoxine were stable in fortified chicken liver and thigh muscle tissues during frozen storage for 1 year at -20 and -70 degrees C. In contrast, the parent compounds depleted approximately 35% in liver tissues at -20 degrees C. The transformation of the depleted sulfa drugs to their N4-glucopyranosyl derivatives was negligible, suggesting that products other than glucosides resulted during the storage period.

Depletion of the monoamino metabolites of Zoalene during frozen storage.

3-Amino-5-nitro-o-toluamide and 5-amino-3-nitro-o-toluamide, the principal metabolites in the tissues of chickens fed a diet containing Zoalene (3,5-dinitro-o-toluamide), were shown to deplete in frozen liver tissues stored up to 1 year at -20 degrees C, but not at -70 degrees C. A slight loss of 5-amino-3-nitro-o-toluamide also occurred in thigh muscle at -20 degrees C. Evidence is presented that demonstrates that the depletion of the metabolites was partially the result of their transformation to glucopyranosyl derivatives; both the alpha- and beta-anomers of the 5-amino-3-nitro-o-toluamide conjugate were observed in liquid chromatograms of tissue extracts.

Liquid chromatography-electrochemical detection of furazolidone and metabolite in extracts of incurred tissues.

One-day-old chicks were raised to maturity on a diet fortified with 0.0055% furazolidone. Analyses of tissue extracts by a liquid chromatographic-electrochemical detection screening procedure for nitro-containing drugs disclosed, in addition to the parent drug, an unidentified metabolite in the liver and breast tissue of the mature birds sacrificed while on the fortified feed.