Cellular and molecular mechanisms of allergic asthma

Molecular Aspects of Medicine, Journal Year: 2021, Volume and Issue: 85, P. 100995 - 100995

Published: Aug. 5, 2021

Asthma is a chronic disease of the airways, which affects more than 350 million people worldwide. It most common in children, affecting at least 30 children and young adults Europe. complex, partially heritable with marked heterogeneity. Its development influenced both by genetic environmental factors. The common, as well characterized subtype asthma allergic eosinophilic asthma, type 2 airway inflammation. prevalence has substantially increased industrialized countries during last 60 years. mechanisms underpinning this phenomenon are incompletely understood, however exposure to various pollutants probably plays role. Disease inception thought be enabled disadvantageous shift balance between protective harmful lifestyle factors, including commensal microbes versus infection pathogens, collectively leading epithelial cell damage disrupted barrier integrity. Epithelial cell-derived cytokines one main drivers immune response against innocuous allergens, ultimately infiltration lung tissue T helper (TH2) cells, innate lymphoid cells (ILC2s), M2 macrophages eosinophils. This review outlines responsible for orchestration inflammation summarizes novel findings, but not limited dysregulated integrity, alarmin release stimulation.

Language: Английский

---

Phenotypic and Transcriptional Changes of Pulmonary Immune Responses in Dogs Following Canine Distemper Virus Infection

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(17), P. 10019 - 10019

Published: Sept. 2, 2022

Canine distemper virus (CDV), a morbillivirus within the family Paramyxoviridae, is highly contagious infectious agent causing multisystemic, devastating disease in broad range of host species, characterized by severe immunosuppression, encephalitis and pneumonia. The present study aimed at investigating pulmonary immune responses CDV-infected dogs situ using immunohistochemistry whole transcriptome analyses bulk RNA sequencing. Spatiotemporal analysis phenotypic changes revealed primarily driven MHC-II+, Iba-1+ CD204+ innate cells during acute subacute infection phases, which paralleled pathologic lesion development coincided with high viral loads lungs. CD20+ B cell numbers initially declined, followed lymphoid repopulation advanced phase. Transcriptome demonstrated an increased expression transcripts related to immunity, antiviral defense mechanisms, type I interferon regulation death lung dogs. Molecular also disturbed cytokine pro-inflammatory M1 macrophage polarization impaired mucociliary exploratory provides detailed data on CDV-related responses, expanding list immunologic parameters potentially leading elimination virus-induced immunopathology canine distemper.

Language: Английский

---

Lipid Nanoparticles as Delivery Vehicles for Inhaled Therapeutics

Biomedicines, Journal Year: 2022, Volume and Issue: 10(9), P. 2179 - 2179

Published: Sept. 2, 2022

Lipid nanoparticles (LNPs) have emerged as a powerful non-viral carrier for drug delivery. With the prevalence of respiratory diseases, particularly highlighted by current COVID-19 pandemic, investigations into applying LNPs to deliver inhaled therapeutics directly lungs are underway. The progress in LNP development well recent pre-clinical studies three main classes encapsulated drugs: small molecules, nucleic acids and proteins/peptides will be discussed. advantages pulmonary delivery system such reducing systemic toxicity enabling higher local concentration evaluated together with challenges design considerations improved formulations. This review provides perspective on future prospects LNP-mediated diseases.

Language: Английский

---

Postprandial parasympathetic signals promote lung type 2 immunity

Neuron, Journal Year: 2025, Volume and Issue: 113(5), P. 670 - 683.e7

Published: Jan. 20, 2025

Language: Английский

---

Lung microbiome and coronavirus disease 2019 (COVID-19): Possible link and implications

Human Microbiome Journal, Journal Year: 2020, Volume and Issue: 17, P. 100073 - 100073

Published: Aug. 1, 2020

Coronavirus disease 2019 (COVID-19) is a rapidly emerging caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The begins as an infection of lungs, which self-limiting in the majority infections; however, some develop distress and organ failures. Lung microbiome, though neglected previously have received interest recently because its association with several diseases immunity. microbiome can modify risk consequences COVID-19 activating innate adaptive immune response. In this review, we examine current evidence on lung how affect SARS-CoV-2 outcomes disease. To date there no direct from human or animal studies role modifying disease; related support that play essential developing immunity against viral infections. Future need to be undertaken find relationship between

Language: Английский

---

No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases

Biological reviews/Biological reviews of the Cambridge Philosophical Society, Journal Year: 2018, Volume and Issue: 93(3), P. 1518 - 1557

Published: March 25, 2018

ABSTRACT Since the successful conquest of many acute, communicable (infectious) diseases through use vaccines and antibiotics, currently most prevalent are chronic progressive in nature, all accompanied by inflammation. These include neurodegenerative (e.g. Alzheimer's, Parkinson's), vascular atherosclerosis, pre‐eclampsia, type 2 diabetes) autoimmune rheumatoid arthritis multiple sclerosis) that may appear to have little common. In fact they share significant features, particular inflammation its attendant inflammatory cytokines. Such effects do not happen without underlying initially ‘external’ causes, it is interest seek these causes. Taking a systems approach, we argue causes ( i ) stress‐induced iron dysregulation, ii ability awaken dormant, non‐replicating microbes with which host has become infected. Other external be dietary. capable shedding small, but functionally amounts highly inflammagenic molecules such as lipopolysaccharide lipoteichoic acid. Sequelae coagulopathies, least recently discovered amyloidogenic clotting blood, leading cell death release further inflammagens. The extensive evidence discussed here implies, was found ulcers, almost chronic, infectious harbour microbial component. What differs simply anatomical location from at exert damage. This analysis offers novel avenues for diagnosis treatment.

Language: Английский

---

Invited Review: From nose to gut – the role of the microbiome in neurological disease

Neuropathology and Applied Neurobiology, Journal Year: 2018, Volume and Issue: 45(3), P. 195 - 215

Published: Oct. 9, 2018

Inflammation and neurodegeneration are key features of many chronic neurological diseases, yet the causative mechanisms underlying these processes poorly understood. There has been mounting interest in role human microbiome modulating inflammatory milieu central nervous system (CNS) health disease. To date, most research focussed on a gut-brain axis, with other mucosal surfaces being relatively neglected. We herein take novel approach comprehensively reviewing roles across several interfaces - nose, mouth, lung gut Parkinson's disease (PD), Alzheimer's (AD) multiple sclerosis (MS). This review systematically appraises anatomical microbiological landscape each surface before considering relevant that may influence initiation progression PD, AD MS. The cumulative effects dysbiosis from nose to contribute significantly through wide variety mechanisms, including direct translocation bacteria their products, modulation systemic or CNS-specific immunity. remains an understudied exciting area for future lead development therapeutic targets

Language: Английский

---

Bacterial-Host Interactions: Physiology and Pathophysiology of Respiratory Infection

Physiological Reviews, Journal Year: 2018, Volume and Issue: 98(2), P. 781 - 811

Published: Feb. 28, 2018

It has long been thought that respiratory infections are the direct result of acquisition pathogenic viruses or bacteria, followed by their overgrowth, dissemination, and in some instances tissue invasion. In last decades, it become apparent contrast to this classical view, majority microorganisms associated with inflammation actually common members ecosystem only rare circumstances do they cause disease. This suggests a complex interplay between host, environment, properties colonizing together determines disease development its severity. To understand pathophysiological processes underlie infectious diseases, is therefore necessary host-bacterial interactions occurring at mucosal surfaces, along microbes inhabiting them, during symbiosis. Current knowledge regarding asymptomatic colonization will be discussed, including plausible role for human microbiome maintaining healthy state. With as starting point, we discuss possible disruptive factors contributing dysbiosis, which likely key trigger pathobionts pathophysiology diseases. Finally, from renewed perspective, reflect on current potential new approaches treatment future.

Language: Английский

---

Fecal microbial transplantation and a high fiber diet attenuates emphysema development by suppressing inflammation and apoptosis

Experimental & Molecular Medicine, Journal Year: 2020, Volume and Issue: 52(7), P. 1128 - 1139

Published: July 1, 2020

Recent work has suggested a microbial dysbiosis association between the lung and gut in respiratory diseases. Here, we demonstrated that microbiome modulation attenuated emphysema development. To modulate microbiome, fecal microbiota transplantation (FMT) diet modification were adopted mice exposed to smoking poly I:C for model. We analyzed severity of by mean linear intercept (MLI) apoptosis fluorescent TUNEL assay. Microbiome analysis was also performed feces extracellular vesicles (EVs). The MLI significantly increased with exposure. FMT or high-fiber (HFD) increase. Weight loss, combined exposure, not noted FMT. HFD decreased macrophages lymphocytes bronchoalveolar lavage fluid. Furthermore, IL-6 IFN-γ fluid serum. score lower HFD, suggesting cell apoptosis. In analysis, Bacteroidaceae Lachnospiraceae, which are alleged metabolize fiber into short-chain fatty acids (SCFAs), at family level HFD. development via local systemic inhibition inflammation changes composition, could provide new paradigm COPD treatment.

Language: Английский

---

Macrophage metabolic reprogramming during chronic lung disease

Mucosal Immunology, Journal Year: 2020, Volume and Issue: 14(2), P. 282 - 295

Published: Nov. 12, 2020

Airway macrophages (AMs) play key roles in the maintenance of lung immune tolerance. Tissue tailored, highly specialised and strategically positioned, AMs are critical sentinels homoeostasis. In last decade, there has been a revolution our understanding how metabolism underlies macrophage functions. While these initial observations were made during steady state or using vitro polarised macrophages, recent studies have indicated that many chronic diseases (CLDs), adapt their metabolic profile to fit local niche. By generating reactive oxygen species (ROS) for pathogen defence, utilising aerobic glycolysis rapidly generate cytokines, employing mitochondrial respiration fuel inflammatory responses, utilise reprogramming host although changes may also support pathology. This review focuses on alterations underlie AM phenotype function CLDs. Particular emphasis is given new plasticity be exploited develop AM-focused therapies.

Language: Английский

---