Jerico del-Rosario

Bio: Jerico del-Rosario is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Asthma & Rhinovirus. The author has an hindex of 3, co-authored 4 publications receiving 436 citations. Previous affiliations of Jerico del-Rosario include Medical Research Council & Imperial College Healthcare.

IL-33–Dependent Type 2 Inflammation during Rhinovirus-induced Asthma Exacerbations In Vivo

Abstract: Rationale: Rhinoviruses are the major cause of asthma exacerbations; however, its underlying mechanisms are poorly understood. We hypothesized that the epithelial cell–derived cytokine IL-33 plays ...

Interleukin-18 Is Associated With Protection Against Rhinovirus-Induced Colds and Asthma Exacerbations

Abstract: Rhinoviruses cause the common cold and exacerbations of asthma. Animal models of infection have identified a protective role for interleukin-18 (IL-18). Following experimental rhinovirus infection, we observed increased respiratory symptoms in healthy and asthmatic subjects with low nasal and bronchial IL-18 levels.

T5 Sampling Airway Mucosal Lining Fluid Identifies Roles For IL-33 and Multiple Inflammatory Pathways in Virus-Induced Asthma Exacerbations

Abstract: Rhinovirus (RV) infection is the most common cause of asthma exacerbations (AE), however mechanisms are poorly understood. Conventional sampling techniques such as bronchoalveolar lavage dilute many cytokines below limits of detection and consequently it has not been possible to measure key mediators of Th1, Th2 and Th17 pathways during virus-induced AE’s . In addition, IL-33, an epithelial-derived alarmin, has recently been shown to be essential for mouse virus-induced airway hyperresponsiveness, however the relationship between IL-33 and exacerbations in human asthma remains unknown. Using the human model of experimental RV induced AE along with novel techniques to sample upper and lower airway mucosal lining fluid (MLF) we investigated the roles of IL-33 and several other prominent cytokines in virus-induced AE’s. Methods 32 mild-to-moderate asthmatics and 14 healthy subjects were inoculated nasally with RV-16. Symptom scores were recorded daily. Bronchoscopies were performed 2 weeks prior to inoculation and on d4 post-inoculation. Novel techniques to sample MLF called ‘bronchosorption’ and ‘nasosorption’ were performed. Cytokines were measured in both bronchial and nasal samples at baseline and on d4 with further nasal sampling on days 2, 3, 5, 7, 10 and 42. Results In asthma, nasal IL-4, –5, –13, –17, –33, and IFN-γ levels were significantly increased during infection compared to baseline (all P Conclusion Sampling MLF permits the direct measurement of previously undetectable mediators across multiple inflammatory pathways. Increased IL-33 and Th2 induction are associated with increased AE severity. IL-33 correlated strongly with Th2 cytokine levels and may represent a novel target for the treatment of virus-induced AE’s. In addition, nasal Th2 inflammation correlated with bronchial levels whilst baseline levels predicted the magnitude of Th2 induction during the AE. Therefore it may be possible to use nasosorption to guide therapy with anti-IL-5 and anti-IL-13 mAb treatments.

Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria (111.33)

Abstract: Macrophages mediate crucial innate immune responses via caspase-1-dependent processing and secretion of IL-1β and IL-18. While wild type Salmonella typhimurium infection is lethal to mice, a strain that persistently expresses flagellin was cleared by the cytosolic flagellin detection pathway via NLRC4 activation of caspase-1; however, this clearance was independent of IL-1β and IL-18. Instead, caspase-1 induced pyroptotic cell death released bacteria from macrophages, exposing them to uptake and killing by reactive oxygen species in neutrophils. Similarly, caspase-1 cleared Legionella and Burkholderia by cytokine independent mechanisms. Our results show, for the first time, that caspase-1 can clear intracellular bacteria in vivo independent of IL-1β and IL-18, and establish pyroptosis as an efficient mechanism of bacterial clearance by the innate immune system.

Risk factors for severe and critically ill COVID-19 patients: A review.

Abstract: The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an unprecedented global social and economic impact, and high numbers of deaths. Many risk factors have been identified in the progression of COVID-19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID-19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high-sensitivity C-reactive protein, proinflammatory cytokines such as interleukin (IL)-6, IL-1β, Krebs von den Lungen-6 (KL-6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID-19.

Interleukin-33 (IL-33): A nuclear cytokine from the IL-1 family

Abstract: Interleukin-33 (IL-33) is a tissue-derived nuclear cytokine from the IL-1 family abundantly expressed in endothelial cells, epithelial cells and fibroblast-like cells, both during homeostasis and inflammation. It functions as an alarm signal (alarmin) released upon cell injury or tissue damage to alert immune cells expressing the ST2 receptor (IL-1RL1). The major targets of IL-33 in vivo are tissue-resident immune cells such as mast cells, group 2 innate lymphoid cells (ILC2s) and regulatory T cells (Tregs). Other cellular targets include T helper 2 (Th2) cells, eosinophils, basophils, dendritic cells, Th1 cells, CD8+ T cells, NK cells, iNKT cells, B cells, neutrophils and macrophages. IL-33 is thus emerging as a crucial immune modulator with pleiotropic activities in type-2, type-1 and regulatory immune responses, and important roles in allergic, fibrotic, infectious, and chronic inflammatory diseases. The critical function of IL-33/ST2 signaling in allergic inflammation is illustrated by the fact that IL33 and IL1RL1 are among the most highly replicated susceptibility loci for asthma. In this review, we highlight 15 years of discoveries on IL-33 protein, including its molecular characteristics, nuclear localization, bioactive forms, cellular sources, mechanisms of release and regulation by proteases. Importantly, we emphasize data that have been validated using IL-33-deficient cells.

Mepolizumab for Severe Eosinophilic Asthma (DREAM): A Multicentre, Double-Blind, Placebo-Controlled Trial

Abstract: ID Pavord, S Korn, P Howarth. Lancet. 2012;380(9842):651–659 To elucidate the efficacy, safety, and patient characteristics of responsiveness to mepolizumab (a humanized monoclonal antibody against interleukin 5). Previous small, proof-of-concept studies in subjects with severe, eosinophilic asthma revealed that mepolizumab decreased exacerbation rates. From 81 multinational centers, 621 pa-tients were enrolled. Major inclusion criteria included: age 12 to 74 years, asthma diagnosis with objective measures, ≥2 asthma exacerbations requiring oral corticosteroids in the last year, refractory asthma as defined by the American …