Food allergy now affects 6%–8% of children in the Western world; despite this, we understand little about why certain people become sensitized to food allergens. The dominant form of food allergy is mediated by food-specific immunoglobulin E (IgE) antibodies, which can cause a variety of symptoms, including life-threatening anaphylaxis. A central step in this immune response to food antigens that differentiates tolerance from allergy is the initial priming of T cells by antigen-presenting cells (APCs), primarily different types of dendritic cells (DCs). DCs, along with monocyte and macrophage populations, dictate oral tolerance versus allergy by shaping the T cell and subsequent B cell antibody response. A growing body of literature has shed light on the conditions under which antigen presentation occurs and how different types of T cell responses are induced by different APCs. We will review APC subsets in the gut and discuss mechanisms of APC-induced oral tolerance versus allergy to food identified using mouse models and patient samples.

Emerging clinical data demonstrates that COVID-19, the disease caused by SARS-CoV2, is a syndrome that variably affects nearly every organ system. Indeed, the clinical heterogeneity of COVID-19 ranges from relatively asymptomatic to severe disease with death resultant from multiple constellations of organ failures. In addition to genetics and host characteristics, it is likely that viral dissemination is a key determinant of disease manifestation. Given the complexity of disease expression, one major limitation in current animal models is the ability to capture this clinical heterogeneity due to technical limitations related to murinizing SARS-CoV2 or humanizing mice to render susceptible to infection. Here we describe a murine model of COVID-19 using respiratory infection with the native mouse betacoronavirus MHV-A59. We find that whereas high viral inoculums uniformly led to hypoxemic respiratory failure and death, lethal dose 50% (LD50) inoculums led to a recapitulation of most hallmark clinical features of COVID-19, including lymphocytopenias, heart and liver damage, and autonomic dysfunction. We find that extrapulmonary manifestations are due to viral metastasis and identify a critical role for type-I but not type-III interferons in preventing systemic viral dissemination. Early, but not late treatment with intrapulmonary type-I interferon, as well as convalescent serum, provided significant protection from lethality by limiting viral dissemination. We thus establish a Biosafety Level II model that may be a useful addition to the current pre-clinical animal models of COVID-19 for understanding disease pathogenesis and facilitating therapeutic development for human translation.

Coronaviruses are a major healthcare threat to humankind. Currently, the host factors that contribute to limit disease severity in healthy young patients are not well defined. Interferons are key antiviral molecules, especially type I and type III interferons. The role of these interferons during coronavirus disease is a subject of debate. Here using mice that are deficient in type I (IFNAR1 -/- ), type III (IFNLR1 -/- ) or both (IFNAR1/LR1 -/- ) interferon signaling pathways and murine adapted coronavirus (MHV-A59) administered through intranasal route, we define the role of interferons in coronavirus infection. We show that type I interferons play a major role in host survival in this model while a minimal role of type III interferons was manifested only in the absence of type I interferons or during a lethal dose of coronavirus. IFNAR1 -/- and IFNAR1/LR1 -/- mice had an uncontrolled viral burden in the airways and lung and increased viral dissemination to other organs. The absence of only type III interferon signaling had no measurable difference in the viral load. The increased viral load in IFNAR1 -/- and IFNAR1/LR1 -/- mice was associated with increased tissue injury, especially evident in the lung and liver. Type I but not type III interferon treatment was able to promote survival if treated during early disease. Further, we show that type I interferon signaling in macrophages contributes to the beneficial effects during coronavirus infection in mice. Importance: The antiviral and pathological potential of type I and type III interferons during coronavirus infection remains poorly defined and opposite findings have been reported. We report that both type I and type III interferons have anti-coronaviral activities, but their potency and organ specificity differ. Type I interferons deficiency rendered the mice susceptible to even a sublethal murine coronavirus infection, while the type III interferon deficiency impaired survival only during a lethal infection or during a sublethal infection in absence of type I interferon signaling. While treatment with both type I and III interferons promoted viral clearance in the airways and lung, only type I interferons promoted the viral clearance in the liver and improved host survival upon early treatment (12 hours post infection). This study demonstrates distinct roles and potency of type I and type III interferons and their therapeutic potential during coronavirus lung infection.

Cirrhosis is among the leading causes of death worldwide, making up 3.5% of global deaths. It is characterized by the replacement of the liver parenchyma with fibrotic tissue and progressively leads to complete failure of the organ. It is classified into 2 types – compensated and decompensated based on the complications such as esophageal varices, hepatic encephalopathy, asterixis, and ascites. The 2 main contributors of the disease include infection and alcohol use and these, in turn, affect 4 main cell types- Hepatic Stellate Cells, Hepatocytes, LSECs, Kupffer Cells. Commonly observed in patients with cirrhosis, stellate cells are characterized by a change in phenotype often seen in wound healing mechanisms and high proliferation whereas the apoptosis of hepatocytes is a key feature leading to inflammation. The polarization of Kupffer Cells leading to the secretion of proinflammatory cytokines is another key cause of cirrhosis and the change from a fenestrated to a smooth, capillarized phenotype is observed in Sinusoidal Endothelial Cells. The role of cirrhosis on the immunology of the liver is another important topic where changes in the concentration of complement proteins, cytokines can affect the number of dendritic cells and in turn, cause pro- and anti-inflammatory responses. Modern treatment for cirrhosis has been shaped based on these cells, complications, and molecules. In this review, we shall discuss all these topics in greater detail along with interesting ideas such as the reversibility of fibrosis as well as the future research on treatments, based on the current findings.

Glioma, a type of tumor arising from the brain and/or spinal cord, is a relatively broad term, encompassing three main types of glial cell tumors: astrocytoma, ependymoma, and oligodendroglioma. A prognosis for a glioma can often be extremely poor, with an overall survival rate of 54.84%. With around 20,000 gliomas being diagnosed each year, it is imperative that effective treatments are developed for management of these tumors. A popular treatment pathway for the treatment of gliomas is surgery along with chemo-radiation therapy such as Temozolomide. This current treatment plan, though, has a moderate effect on lengthening glioma patients’ prognoses. The average survival of this plan is 3 to 6 months. New treatments in the field of immunotherapies may have promising effects for glioma patients’ prognoses. Arising developments in immunotherapy glioma treatment and management is an important field to investigate to further improve the effectivity of cancer treatment for glioma patients. Certain immunotherapies in trials have proven to make impactful improvements to glioma prognoses, one trial showing an increase of 2 months in median survival. This literature review will focus on the pathology and characteristics of the proliferation of malignant glioma cells and the role immunotherapy plays in combatting glioma proliferation