Airway innate immunity

Asthma is a high-risk disease based on airway hyperresponsiveness (AHR). In this review, we found that there are many studies on clinical therapy for asthma that focus on the efficacy of acupuncture therapy and its mechanisms, including the functional connectivity of different brain regions, with the aid of functional magnetic resonance imaging (fMRI), immune responses/cell recognition (innate lymphoid cells and balance of Th1/Th2 and Treg/Th17), intracellular mechanism (autophagy, endoplasmic reticulum stress, and epigenetic alteration), and ligand-receptor/chemical signaling pathway (neurotransmitter, hormone, and small molecules)...

BACKGROUND: Trained immunity results in long-term immunological memory, provoking a faster and greater immune response when innate immune cells encounter a secondary, often heterologous, stimulus. We have previously shown that house dust mite (HDM)-induced innate training is amplified in mice expressing the human macrophage migration inhibitory factor (MIF) CATT7 functional polymorphism. AIM: This study investigated the ability of mesenchymal stromal cells (MSCs) to modulate MIF-driven trained immunity both in vitro and in vivo...

Airway epithelium represents a physical barrier against toxic substances and pathogens but also presents pattern recognition receptors on the epithelial cells that detect pathogens leading to molecule release and sending signals that activate both the innate and adaptive immune responses. Thus, impaired airway epithelial function and poor integrity may increase the recurrence of infections. Probiotic use in respiratory diseases as adjuvant of traditional therapy is increasingly widespread. There is growing interest in the use of non-viable heat-killed bacteria, such as tyndallized bacteria (TB), due to safety concerns and to their immunomodulatory properties...

Bronchial asthma is a chronic airway inflammatory disease that involves various immune cells. As the main roles in asthma immune mechanism, T lymphocytes [T helper type 1(Th1) cells, Th2 cells, Th17 cells, regulatory T cells (Tregs), T follicular helper (Tfh) cells and cytotoxic T (Tc) cells], innate lymphoid cells (ILCs), B cells, granulocytes (mast cells, eosinophils, basophils, neutrophils), macrophages as well as dendritic cells (DC) are activated by allergens and secrete their own specific cytokines. They interact with each other in function and form a complex asthma-related immune cell interaction network system...

The concept of immune cell exhaustion/dysfunction has developed mainly to understand impaired type 1 immune responses especially by CD8 T cells against tumors or virus-infected cells and has been applied to other lymphocytes. Natural killer (NK) cells and CD4 T cells support the efficient activation of CD8 T cells but exhibit a dysfunctional phenotype in tumor microenvironments and in chronic virus infections. In contrast, the concept of type 2 immune cell exhaustion/dysfunction is poorly established. Group 2 innate lymphoid cells (ILC2s) and T-helper 2 (Th2) cells are the major lymphocyte subsets that initiate and expand type 2 immune responses for antiparasitic immunity or allergy...

The respiratory effects of particulate matter (PM) in subway station platforms or tunnels have attracted considerable research attention. However, no studies have characterized the effects of subway PM on allergic immune responses. In this study, iron oxide (α-Fe2 O3 and Fe3 O4 ) particles-the main components of subway PM-were intratracheally administered to BALB/c mice where ovalbumin (OVA) induced allergic pulmonary inflammation. Iron oxide particles enhanced OVA-induced eosinophil recruitment around the bronchi and mucus production from airway epithelium...

BACKGROUND: Obstructive sleep apnea (OSA) has been linked to cytokine-mediated chronic inflammatory states. Continuous positive airway pressure (CPAP) is an established therapy for OSA, but its effects on inflammation remain unclear. A recent study from our group identified soluble cytokine receptors altered in OSA patients and modified by CPAP adherence. However, the upstream regulatory pathways responsible for these shifts in proinflammatory cascades with OSA and CPAP therapy remained unknown...

BACKGROUND: Repeated exposure to recombinant profilin from Acanthamoeba (rAc-PF) induces allergic airway responses in vitro and in vivo. Based on the role of toll-like receptors (TLRs) in allergic airway diseases, TLRs play a central role in innate immune responses and the adaptive immune system and regulate responses against antigens through antigen-specific receptors. In this study, we attempted to determine the molecular mechanisms underlying rAc-PF-induced allergic inflammatory responses...

BACKGROUND: The interleukin-2 (IL-2) family of cytokines, including IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21, are pivotal regulators of the immune response, impacting both innate and adaptive immunity. Understanding their molecular characteristics, receptor interactions, and signalling pathways is essential for elucidating their roles in health and disease. OBJECTIVES: This review provides a comprehensive overview of the IL-2 family of cytokines, highlighting their molecular biology, receptor interactions, and signalling mechanisms...

All respiratory viruses establish primary infections in the nasal epithelium, where efficient innate immune induction may prevent dissemination to the lower airway and thus minimize pathogenesis. Human coronaviruses (HCoVs) cause a range of pathologies, but the host and viral determinants of disease during common cold versus lethal HCoV infections are poorly understood. We model the initial site of infection using primary nasal epithelial cells cultured at an air-liquid interface (ALI). HCoV-229E, HCoV-NL63, and human rhinovirus-16 are common cold-associated viruses that exhibit unique features in this model: early induction of antiviral interferon (IFN) signaling, IFN-mediated viral clearance, and preferential replication at nasal airway temperature (33 °C) which confers muted host IFN responses...

INTRODUCTION: Chronic rejection is a major complication post-transplantation. Within lung transplantation, chronic rejection was considered as airway centred. Chronic Lung Allograft Dysfunction (CLAD), defined to cover all late chronic complications, makes it more difficult to understand chronic rejection from an immunological perspective. This study investigated the true nature, timing and location of chronic rejection as a whole, within mouse lung transplantation. METHODS: 40 mice underwent an orthotopic left lung transplantation, were sacrificed at day 70 and evaluated by histology and in vivo µCT...

Epithelial cells form a resilient barrier and orchestrate defensive and reparative mechanisms to maintain tissue stability. This review focuses on gut and airway epithelia, which are positioned where the body interfaces with the outside world. We review the many signaling pathways and mechanisms by which epithelial cells at the interface respond to invading pathogens to mount an innate immune response and initiate adaptive immunity and communicate with other cells, including resident microbiota, to heal damaged tissue and maintain homeostasis...

Group 2 innate lymphoid cells (ILC2s) rapidly induce a type 2 inflammation in the lungs in response to allergens. Here, we focused on the role of iron, a critical nutritional trace element, on ILC2 function and asthma pathogenesis. We found that transferrin receptor 1 (TfR1) is rapidly up-regulated and functional during ILC2 activation in the lungs, and blocking transferrin uptake reduces ILC2 expansion and activation. Iron deprivation reprogrammed ILC2 metabolism, inducing a HIF-1α-driven up-regulation of glycolysis and inhibition of oxidative mitochondrial activity...

Toll-like receptor 5 (TLR5) signaling plays a key role in antibacterial defenses. We previously showed that respiratory administration of flagellin, a potent TLR5 agonist, in combination with amoxicillin improves the treatment of primary pneumonia or superinfection caused by amoxicillin-sensitive or -resistant Streptococcus pneumoniae. Here, the impact of adjunct flagellin therapy on antibiotic dose/regimen and the selection of antibiotic-resistant S. pneumoniae was investigated using superinfection with isogenic antibiotic-sensitive and -resistant bacteria and population dynamics analysis...

The house dust mite (HDM) represents a major cause of allergic rhinitis and asthma. We tested whether HDM-induced aeroallergen exposure sensitivity is caused by the innate-immune response in small airway epithelial cells. HDM exposure rapidly activates NFkB/RelA in the Secretoglobin (Scgb1a1+) lineage and upregulates markers of epithelial plasticity. To determine the effect of epithelial NFkB signaling, NFkB was depleted in a tamoxifen (TMX)-inducible Scgb1a1 -CreERTM mouse within a CL57B/L6 background. Corn oil or TMX-treated/RelA-depleted (RelA KD) mice were repetitively exposed to airway HDM challenges to induce airway hyperresponsiveness (AHR)...

Chronic obstructive pulmonary disease (COPD) is a condition characterized by chronic airway inflammation and obstruction, primarily caused by tobacco smoking. Although the involvement of immune cells in COPD pathogenesis is well established, the contribution of innate lymphoid cells (ILC) remains poorly understood. ILC are a type of innate immune cells that participate in tissue remodeling processes, but their specific role in COPD has not been fully elucidated. During COPD, the breakdown of pulmonary elastin generates elastin peptides that elicit biological activities on immune cells...

BACKGROUND: Excessive inflammation and recurrent airway infections characterize people with cystic fibrosis (pwCF), a disease with highly heterogeneous clinical outcomes. How the overall immune response is affected in pwCF, its relationships with the lung microbiome, and the source of clinical heterogeneity have not been fully elucidated. METHODS: Peripheral blood and sputum samples were collected from 28 pwCF and an age-matched control group. Systemic immune cell subsets and surface markers were quantified using multiparameter flow cytometry...

BACKGROUND: The effects of inhaled corticosteroids (ICS) on healthy airways are poorly defined. OBJECTIVES: To delineate the effects of ICS on gene expression in healthy airways, without confounding caused by changes in disease-related genes and disease-related alterations in ICS responsiveness. METHODS: Randomized open-label bronchoscopy study of high-dose ICS therapy in 30 healthy adult volunteers randomized 2:1 to (i) fluticasone propionate 500 mcg bd daily or (ii) no treatment, for 4 weeks...

Significant advancements have been achieved in understanding the roles of different immune cells, as well as cytokines and chemokines, in the pathogenesis of eosinophilic airway conditions. This review examines the pathogenesis of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), marked by complex immune dysregulation, with major contributions from type 2 inflammation and dysfunctional airway epithelium. The presence of eosinophils and the role of T-cell subsets, particularly an imbalance between Treg and Th17 cells, are crucial to the disease's pathogenesis...

Idiopathic pulmonary fibrosis (IPF) is a morbid fibrotic lung disease with limited treatment options. The pathophysiology of IPF remains poorly understood, and elucidation of the cellular and molecular mechanisms of IPF pathogenesis is key to the development of new therapeutics. B-1 cells are an innate B cell population which play an important role linking innate and adaptive immunity. B-1 cells spontaneously secrete natural IgM and prevent inflammation in several disease states. One class of these IgM recognize oxidation-specific epitopes (OSE), which have been shown to be generated in lung injury and to promote fibrosis...