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Airway innate immunity

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https://www.readbyqxmd.com/read/28078853/oxidative-stress-in-asthma-a-distinct-clinical-and-pathologic-feature
#1
Y Li, G P Li
Asthma is a type of chronic airway inflammation. Corticosteroids are inadequate for asthma therapy. However, it remains unclear whether oxidative stress is a distinct clinical and pathologic feature in asthma. We reviewed the articles on asthma-associated oxidative stress. The exposures to airborne allergens, such as house dust mite (HDM) and birch pollen, may not only trigger innate and adaptive immune responses but also cause oxidative stress damage in the airways. Allergen-induced reactive oxygen species (ROS) is involved in p38 MAPK, phosphoinositide-3-kinase (PI3K)/Akt and nuclear factor erythroid 2-related factor (Nrf2) kinase pathway signaling...
October 2016: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28077651/bromodomain-containing-4-brd4-couples-nf%C3%AE%C2%BAb-rela-with-airway-inflammation-and-the-irf-rig-i-amplification-loop-in-respiratory-syncytial-virus-infection
#2
Bing Tian, Jun Yang, Yingxin Zhao, Teodora Ivanciuc, Hong Sun, Roberto P Garofalo, Allan R Brasier
: The airway mucosa expresses protective interferon (IFN) and inflammatory cytokines in response to Respiratory Syncytial Virus (RSV) infection. In this study, we examine the role of bromodomain containing 4 (BRD4) in mediating this innate immune response in human small airway epithelial cells. We observe that RSV induces BRD4 to complex with NFκB/RelA. BRD4 is functionally required for expression of the NFκB-dependent inflammatory gene regulatory network (GRN), including the IFN Response Factor (IRFs)-1 and -7 that mediate a cross-talk pathway for RIG-I upregulation...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28070196/airway-autoimmune-responses-in-severe-eosinophilic-asthma-following-low-dose-mepolizumab-therapy
#3
Manali Mukherjee, Hui Fang Lim, Sruthi Thomas, Douglas Miller, Melanie Kjarsgaard, Bruce Tan, Roma Sehmi, Nader Khalidi, Parameswaran Nair
BACKGROUND: Anti-interleukin (IL)-5 monoclonal antibodies as an eosinophil-depleting strategy is well established, with Mepolizumab being the first biologic approved as an adjunct treatment for severe eosinophilic asthma. CASE PRESENTATION: A 62-year old woman diagnosed with severe eosinophilic asthma showed poor response to Mepolizumab therapy (100 mg subcutaneous dose/monthly) and subsequent worsening of symptoms. The treatment response to Mepolizumab was monitored using both blood and sputum eosinophil counts...
2017: Allergy, Asthma, and Clinical Immunology
https://www.readbyqxmd.com/read/28069067/end-stage-cystic-fibrosis-lung-disease-is-characterised-by-a-diverse-inflammatory-pattern-an-immunohistochemical-analysis
#4
Elise J Lammertyn, Elly Vandermeulen, Hannelore Bellon, Stephanie Everaerts, Stijn E Verleden, Kathleen Van Den Eynde, Ken R Bracke, Guy G Brusselle, Pieter C Goeminne, Erik K Verbeken, Bart M Vanaudenaerde, Lieven J Dupont
BACKGROUND: Cystic fibrosis (CF) lung disease is characterised by vigorous airway inflammation eventually resulting in severe lung damage. This study aimed to describe the diversity of the inflammatory pattern in end-stage CF lungs by evaluating and quantifying which components of the innate and adaptive immunity are involved, and by assessing whether this is gender-specific. METHODS: CF explant lung tissue (n = 20) collected at time of transplantation and control tissue (n = 22) was sectioned (9 μm) and stained for neutrophils, eosinophils, mast cells, dendritic cells, macrophages, CD4 T cells, cytotoxic T cells and B cells...
January 10, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28063043/subcutaneous-and-sublingual-immunotherapy-in-a-mouse-model-of-allergic-asthma
#5
Laura Hesse, Martijn C Nawijn
Allergic asthma, caused by inhaled allergens such as house dust mite or grass pollen, is characterized by reversible airway obstruction, associated with an eosinophilic inflammation of the airways, as well as airway hyper responsiveness and remodeling. The inhaled allergens trigger a type-2 inflammatory response with involvement of innate lymphoid cells (ILC2) and Th2 cells, resulting in high production of immunoglobulin E (IgE) antibodies. Consequently, renewed allergen exposure results in a classic allergic response with a distinct early and late phase, both resulting in bronchoconstriction and shortness of breath...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28044311/effects-of-hypercapnia-on-the-lung
#6
Masahiko Shigemura, Emilia Lecuona, Jacob I Sznajder
Gases are sensed by lung cells and can activate specific intracellular signaling pathways, and thus have physiologic and pathophysiologic effects. Carbon dioxide (CO2 ), a primary product of oxidative metabolism, can be sensed by eukaryotic cells eliciting specific responses via recently identified signaling pathways. However, the physiological and pathophysiological effects of high CO2 (hypercapnia) on the lungs and specific lung cells, which are the primary site of CO2 elimination, are incompletely understood...
January 3, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28036144/revisiting-type-2-high-and-type-2-low-airway-inflammation-in-asthma-current-knowledge-and-therapeutic-implications
#7
Douglas Robinson, Marc Humbert, Roland Buhl, Alvaro A Cruz, Hiromasa Inoue, Stephan Korom, Nicola A Hanania, Parameswaran Nair
Asthma is a complex respiratory disorder characterized by marked heterogeneity in individual patient disease triggers and response to therapy. Several asthma phenotypes have now been identified, each defined by a unique interaction between genetic and environmental factors, including inflammatory, clinical and trigger-related phenotypes. Endotypes further describe the functional or pathophysiologic mechanisms underlying the patient's disease. Type 2-driven asthma is an emerging nomenclature for a common subtype of asthma and is characterized by the release of signature cytokines IL-4, IL-5 and IL-13 from cells of both the innate and adaptive immune systems...
December 30, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28018859/autophagy-tgf-%C3%AE-and-smad-2-3-signaling-regulates-interferon-%C3%AE-response-in-respiratory-syncytial-virus-infected-macrophages
#8
Swechha M Pokharel, Niraj K Shil, Santanu Bose
Human respiratory syncytial virus (RSV) is a lung tropic virus causing severe airway diseases including bronchiolitis and pneumonia among infants, children, and immuno-compromised individuals. RSV triggers transforming growth factor-β (TGF-β) production from lung epithelial cells and TGF-β facilitates RSV infection of these cells. However, it is still unknown whether RSV infected myeloid cells like macrophages produce TGF-β and the role of TGF-β if any during RSV infection of these cells. Our study revealed that RSV infected macrophages produce TGF-β and as a consequence these cells activate TGF-β dependent SMAD-2/3 signaling pathway...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27992060/cb2-receptors-regulate-natural-killer-cells-that-limit-allergic-airway-inflammation-in-a-murine-model-of-asthma
#9
M E Ferrini, S Hong, A Stierle, D Stierle, N Stella, K Roberts, Z Jaffar
BACKGROUND: Allergic asthma is a chronic airway inflammatory disease involving the complementary actions of innate and adaptive immune responses. Endogenously generated cannabinoids, acting via CB2 receptors play important roles in both homeostatic and inflammatory processes. However, the contribution of CB2-acting eicosanoids to the innate events preceding sensitization to the common house dust mite (HDM) allergen, remain to be elucidated. We investigated the role of CB2 activation during allergen-induced pulmonary inflammation and NK cell effector function...
December 19, 2016: Allergy
https://www.readbyqxmd.com/read/27965936/pseudomonas-aeruginosa-airway-infection-recruits-and-modulates-neutrophilic-myeloid-derived-suppressor-cells
#10
Hasan H Öz, Benyuan Zhou, Pina Voss, Melanie Carevic, Carolin Schroth, Nina Frey, Nikolaus Rieber, Andreas Hector, Dominik Hartl
Pseudomonas aeruginosa is an opportunistic pathogen that causes infections mainly in patients with cystic fibrosis (CF) lung disease. Despite innate and adaptive immune responses upon infection, P. aeruginosa is capable of efficiently escaping host defenses, but the underlying immune mechanisms remain poorly understood. Myeloid-derived suppressor cells (MDSCs) are innate immune cells that are functionally characterized by their potential to suppress T- and natural killer (NK)-cell responses. Here we demonstrate, using an airway in vivo infection model, that P...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27940028/viral-bacterial-co-infections-in-the-respiratory-tract
#11
REVIEW
Lauren O Bakaletz
Preceding or concurrent viral respiratory tract infection can predispose to secondary bacterial co-infection throughout the airway. The mechanisms by which viruses promote these superinfections are diverse and replete. Whereas we understand much as to how viruses damage the airway and dysregulate both innate and acquired immune responses which, in turn, supports bacterial growth, adherence and invasion into normally sterile sites within the respiratory tract, new information regarding these co-infections is being gained from recent advances in microbiome research and our enhanced appreciation of the contribution of bacterial biofilms, among others...
December 7, 2016: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/27935538/the-correlation-of-tas2r38-gene-variants-with-higher-risk-for-chronic-rhinosinusitis-in-polish-patients
#12
Karolina Dżaman, Mariola Zagor, Elżbieta Sarnowska, Antoni Krzeski, Ireneusz Kantor
BACKGROUND: Bitter taste receptors (T2Rs), especially T2R38s appear as innovative regulators of innate immunity in the respiratory system. The single nucleotide polymorphisms (SNPs) in TAS2R38 gene may contribute to individual differences in susceptibility to respiratory infections especially chronic rhinosinusitis (CRS). TAS2R38 genotypes distribution varies by geographic region, race and ethnicity. The aim of the preliminary study was the identification of SNPs in TAS2R38 encoding genes in Polish patients with CRS and finding potential correlation with CRS phenotypes...
October 31, 2016: Otolaryngologia Polska. the Polish Otolaryngology
https://www.readbyqxmd.com/read/27895643/azithromycin-attenuates-pseudomonas-induced-lung-inflammation-by-targeting-bacterial-proteins-secreted-in-the-cultured-medium
#13
Teresinha Leal, Gabriella Bergamini, François Huaux, Nadtha Panin, Sabrina Noel, Barbara Dhooghe, Jeremy B Haaf, Pierluigi Mauri, Sara Motta, Dario Di Silvestre, Paola Melotti, Claudio Sorio
BACKGROUND: Pseudomonas aeruginosa airway infections are a major cause of morbidity and mortality in patients with cystic fibrosis (CF). Azithromycin improves the related clinical outcomes, but its mechanisms of action remain poorly understood. We tested the hypothesis that azithromycin downregulates P. aeruginosa-induced pro-inflammatory responses by modifying release of bacterial proteins. METHODS: We monitored inflammatory markers in lungs of CF mutant mice and their littermate controls in response to conditioned media (CM) collected from the reference P...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27895167/pgi2-controls-pulmonary-nk-cells-that-prevent-airway-sensitization-to-house-dust-mite-allergen
#14
Bryan Simons, Maria E Ferrini, Sophia Carvalho, David J P Bassett, Zeina Jaffar, Kevan Roberts
In allergic asthma, inhalation of airborne allergens such as the house dust mite (HDM) effectively activates both innate and adaptive immunity in the lung mucosa. To determine the role of the eicosanoid PGI2 and its receptor IP during allergic airway sensitization, HDM responses in mice lacking a functional IP receptor (i.e., PGI2 IP receptor-deficient [IP(-/-)]) were compared with wild type (WT) mice. Surprisingly, IP(-/-) mice had increased numbers of pulmonary CD3(-)NK1.1(+)Ly49b(+) NK cells producing IFN-γ that was inversely associated with the number of type 2 innate lymphoid cells (ILC2s) expressing IL-33Rα and IL-13 compared with WT animals...
January 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27894811/critical-role-of-toll-like-receptors-in-pathophysiology-of-allergic-asthma
#15
Seyyed Shamsadin Athari, Seyyede Masoume Athari, Fateme Beyzay, Masoud Movassaghi, Esmaeil Mortaz, Mehdi Taghavi
Allergic asthma is an airway disease, characterized by reversible bronchoconstriction, chronic inflammation of the airway, and thickness of smooth muscle in the respiratory tract. Asthma is orchestrated by an excessive Th2-adaptive immune response, in which innate immunity plays a key role. Recently TLRs have received more and more attention as they are central to orchestrate the innate immune responses. TLRs are localized as integral membrane or intracellular glycoproteins with those on the cell surface sensing microbial antigens and the ones, localized in intracellular vesicles, sensing microbial nucleic acid species...
November 26, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27871304/respiratory-viral-infections-and-host-responses-insights-from-genomics
#16
REVIEW
Niamh M Troy, Anthony Bosco
Respiratory viral infections are a leading cause of disease and mortality. The severity of these illnesses can vary markedly from mild or asymptomatic upper airway infections to severe wheezing, bronchiolitis or pneumonia. In this article, we review the viral sensing pathways and organizing principles that govern the innate immune response to infection. Then, we reconstruct the molecular networks that differentiate symptomatic from asymptomatic respiratory viral infections, and identify the underlying molecular drivers of these networks...
November 21, 2016: Respiratory Research
https://www.readbyqxmd.com/read/27870227/aspergillosis-and-the-role-of-mucins-in-cystic-fibrosis
#17
REVIEW
Abigail C Cowley, David J Thornton, David W Denning, Alexander Horsley
The prevalence of aspergillosis in CF patients has until recently been underestimated, but increasing evidence suggests that it may play an important role in the progression of CF lung disease. In healthy airways, Aspergillus fumigatus can be efficiently removed from the lung by mechanisms such as mucociliary clearance and cough. However, these mechanisms are defective in CF, allowing pathogens such as A. fumigatus to germinate and establish chronic infections within the airways. The precise means by which A...
November 21, 2016: Pediatric Pulmonology
https://www.readbyqxmd.com/read/27868161/neutrophil-plasticity-enables-the-development-of-pathological-microenvironments-implications-for-cystic-fibrosis-airway-disease
#18
REVIEW
Camilla Margaroli, Rabindra Tirouvanziam
INTRODUCTION: The pathological course of several chronic inflammatory diseases, including cystic fibrosis, chronic obstructive pulmonary disease, and rheumatoid arthritis, features an aberrant innate immune response dominated by neutrophils. In cystic fibrosis, neutrophil burden and activity of neutrophil elastase in the extracellular fluid have been identified as strong predictors of lung disease severity. REVIEW: Although neutrophils are generally considered to be rigid, pre-programmed effector leukocytes, recent studies suggest extensive plasticity in how neutrophil functions unfold upon recruitment to peripheral tissues, and how they choose their ultimate fate...
December 2016: Molecular and Cellular Pediatrics
https://www.readbyqxmd.com/read/27858144/th9-and-other-il-9-producing-cells-in-allergic-asthma
#19
REVIEW
Sonja Koch, Nina Sopel, Susetta Finotto
Allergic asthma is a worldwide increasing chronic disease of the airways which affects more than 300 million people. It is associated with increased IgE, mast cell activation, airway hyperresponsiveness (AHR), mucus overproduction and remodeling of the airways. Previously, this pathological trait has been associated with T helper type 2 (Th2) cells. Recently, different CD4(+) T cell subsets (Th17, Th9) as well as cells of innate immunity, like mast cells and innate lymphoid cells type 2 (ILC2s), which are all capable of producing the rediscovered cytokine IL-9, are known to contribute to this disease...
November 17, 2016: Seminars in Immunopathology
https://www.readbyqxmd.com/read/27848994/the-host-genetic-background-defines-diverse-immune-reactivity-and-susceptibility-to-chronic-pseudomonas-aeruginosa-respiratory-infection
#20
Lorenza Spagnuolo, Maura De Simone, Nicola Ivan Lorè, Ida De Fino, Veronica Basso, Anna Mondino, Cristina Cigana, Alessandra Bragonzi
Patients with P. aeruginosa airways infection show markedly variable clinical phenotypes likely influenced by genetic backgrounds. Here, we investigated the cellular events involved in resistance and susceptibility to P. aeruginosa chronic infection using genetically distinct inbred mouse strains. As for patients, different murine genotypes revealed variable susceptibility to infection. When directly compared, resistant C3H/HeOuJ and susceptible A/J strains revealed distinct immune responsiveness to the pathogen...
November 16, 2016: Scientific Reports
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