ABSTRACT
Viral infection makes us feel sick as the immune system alters systemic metabolism to better fight the pathogen. The extent of these changes is relative to the severity of disease. Whether blood glucose is subject to infection-induced modulation is mostly unknown. Here we show that strong, nonlethal infection restricts systemic glucose availability, which promotes the antiviral type I interferon (IFN-I) response. Following viral infection, we find that IFNγ produced by γδ T cells stimulates pancreatic ß cells to increase glucose-induced insulin release. Subsequently, hyperinsulinemia lessens hepatic glucose output. Glucose restriction enhances IFN-I production by curtailing lactate-mediated inhibition of IRF3 and NF-κB signaling. Induced hyperglycemia constrained IFN-I production and increased mortality upon infection. Our findings identify glucose restriction as a physiological mechanism to bring the body into a heightened state of responsiveness to viral pathogens. This immune-endocrine circuit is disrupted in hyperglycemia, possibly explaining why patients with diabetes are more susceptible to viral infection.
Subject(s)
Blood Glucose , Immunity, Innate , Interferon-gamma , Animals , Interferon-gamma/metabolism , Interferon-gamma/immunology , Mice , Blood Glucose/metabolism , Insulin-Secreting Cells/immunology , Insulin-Secreting Cells/metabolism , Mice, Inbred C57BL , Signal Transduction/immunology , Insulin/metabolism , Insulin/immunology , Mice, Knockout , Hyperglycemia/immunology , Interferon Regulatory Factor-3/metabolism , NF-kappa B/metabolism , Humans , Liver/immunology , Liver/virology , Liver/metabolism , MaleABSTRACT
Cancer of the urinary bladder is a neoplasm with considerable importance in veterinary medicine, given its high incidence in several domestic animal species and its life-threatening character. Bladder cancer in companion animals shows a complex and still poorly understood biopathology, and this lack of knowledge has limited therapeutic progress over the years. Even so, important advances concerning the identification of tumour markers with clinical applications at the diagnosis, prognosis and therapeutic levels have recently been made, for example, the identification of pathological BRAF mutations. Those advances are now facilitating the introduction of targeted therapies. The present review will address such advances, focusing on small animal oncology and providing the reader with an update on this field. When appropriate, comparisons will be drawn with bladder cancer in human patients, as well as with experimental models of the disease.
ABSTRACT
The importance of immune cells present in the adipose tissue to metabolic homeostasis has been increasingly recognized. Nevertheless, in bovines few studies have so far addressed the immune cell populations resident in this tissue. Here we developed an eight-colour flow cytometry panel to address T cell populations present in bovine adipose tissue. Our results showed that γδ T cells, CD4+ and CD8+ CD3+ non-γδ T cells, as well as NK cells, are present in the mesenteric and subcutaneous adipose tissue of Holstein-Friesian cows. The frequency of both γδ T cells and CD8+ non-γδ T cells was found higher in mesenteric than in subcutaneous adipose tissue. The majority of T cells in adipose tissue presented a CD45RO+CD62L- phenotype, characteristic of effector memory cells, and the frequency of these cellular populations was higher than in the blood. The ratio of CD4+ T cells over CD8+ T cells was similar between subcutaneous and mesenteric adipose tissue but different from the one found in blood. Overall, our results highlight particular phenotypic characteristics of bovine adipose tissue T cell populations.
