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Airway innate immunity

Yi-Lin Zhang, Peng-Xiao Chen, Wei-Jie Guan, Hong-Mei Guo, Zhuo-Er Qiu, Jia-Wen Xu, Yu-Li Luo, Chong-Feng Lan, Jian-Bang Xu, Yuan Hao, Ya-Xia Tan, Ke-Nan Ye, Zhao-Rong Lun, Lei Zhao, Yun-Xin Zhu, Jiehong Huang, Wing-Hung Ko, Wei-De Zhong, Wen-Liang Zhou, Nan-Shan Zhong
Airway epithelial cells harbor the capacity of active Cl- transepithelial transport and play critical roles in modulating innate immunity. However, whether intracellular Cl- accumulation contributes to relentless airway inflammation remains largely unclear. This study showed that, in airway epithelial cells, intracellular Cl- concentration ([Cl- ]i ) was increased after Pseudomonas aeruginosa lipopolysaccharide (LPS) stimulation via nuclear factor-κB (NF-κB)-phosphodiesterase 4D (PDE4D)-cAMP signaling pathways...
March 15, 2018: Mucosal Immunology
Marie Pariollaud, Julie Gibbs, Thomas Hopwood, Sheila Brown, Nicola Begley, Ryan Vonslow, Toryn Poolman, Baoqiang Guo, Ben Saer, D Heulyn Jones, James P Tellam, Stefano Bresciani, Nicholas Co Tomkinson, Justyna Wojno-Picon, Anthony Wj Cooper, Dion A Daniels, Ryan P Trump, Daniel Grant, William Zuercher, Timothy M Willson, Andrew S MacDonald, Brian Bolognese, Patricia L Podolin, Yolanda Sanchez, Andrew Si Loudon, David W Ray
Recent studies reveal that airway epithelial cells are critical pulmonary circadian pacemaker cells, mediating rhythmic inflammatory responses. Using mouse models, we now identify the rhythmic circadian repressor REV-ERB as essential to the mechanism coupling the pulmonary clock to innate immunity, involving both myeloid, and bronchial epithelial cells in temporal gating and determining amplitude of response to inhaled endotoxin. Dual mutation of REV-ERBα and its paralog REV-ERBβ in bronchial epithelia further augmented inflammatory responses and chemokine activation, but also initiated a basal inflammatory state, revealing a critical homeostatic role for REV-ERB proteins in the suppression of the endogenous pro-inflammatory mechanism in un-challenged cells...
March 13, 2018: Journal of Clinical Investigation
Masakatsu Yamashita, Makoto Kuwahara
Although Bach2 (broad complex-tramtrack-bric a brac and Cap'n'collar homology 2) plays an important role in regulating Th2 cell differentiation and type-2 immune responses, the underlying molecular mechanisms remain unclear. Our current studies demonstrate that Bach2 associates with Batf (basic leucine zipper transcription factor ATF-like) family transcription factors and binds to the regulatory regions of the Th2 cytokine gene loci. The Bach2-Batf complex antagonizes the recruitment of the interferon regulatory factor 4 (Irf4)-containing Batf complex to activator protein 1 (AP-1) motifs in the Th2 cytokine gene locus and suppresses Th2 cytokine production and/or Th2 cell differentiation...
February 24, 2018: International Immunology
Clare A Stokes, Alison M Condliffe
Defining features of chronic airway diseases include abnormal and persistent inflammatory processes, impaired airway epithelial integrity and function, and increased susceptibility to recurrent respiratory infections. Phosphoinositide 3-kinases (PI3K) are lipid kinases, which contribute to multiple physiological and pathological processes within the airway, with abnormal PI3K signalling contributing to the pathogenesis of several respiratory diseases. Consequently, the potential benefit of targeting PI3K isoforms has received considerable attention, being viewed as a viable therapeutic option in inflammatory and infectious lung disorders...
March 9, 2018: Biochemical Society Transactions
Charu Rajput, Megan P Walsh, Breanna N Eder, Ediri E Metitiri, Antonia P Popova, Marc B Hershenson
Infections with rhinovirus (RV) cause asthma exacerbations. Recent studies suggest that macrophages play a role in asthmatic airway inflammation and the innate immune response to RV infection. Macrophages exhibit discrete phenotypes based on surface markers and gene expression. We hypothesized that macrophage polarization state alters gene expression in response to RV infection. Cells were derived from human peripheral blood derived monocytes. M1 and M2 polarization was carried out using IFN-y and IL-4, respectively, and RNA was extracted for Affymetrix Human Gene ST2...
March 9, 2018: Physiological Genomics
Yang Liu, Yin Yao, Zhi-Chao Wang, Qing Ning, Zheng Liu
Host immunity (innate and adaptive immunity) plays essential roles in the pathogenesis of inflammatory upper airway diseases including allergic rhinitis and chronic rhinosinusitis. Recently, the discovery of novel innate immune cells, particularly innate lymphoid cells, has renewed our view on the role of innate immunity in inflammatory upper airway diseases. Meanwhile, the identification of new subsets of T helper (Th) cells including Th22, Th9 and follicular Th cells, and regulatory B cells in the adaptive immunity has broadened our knowledge on the complex immune networks in inflammatory upper airway diseases...
March 7, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Sabine Stegemann-Koniszewski, Sarah Behrens, Julia D Boehme, Inga Hochnadel, Peggy Riese, Carlos A Guzmán, Andrea Kröger, Jens Schreiber, Matthias Gunzer, Dunja Bruder
The innate immune system senses influenza A virus (IAV) through different pathogen-recognition receptors including Toll-like receptor 7 (TLR7). Downstream of viral recognition natural killer (NK) cells are activated as part of the anti-IAV immune response. Despite the known decisive role of TLR7 for NK cell activation by therapeutic immunostimulatory RNAs, the contribution of TLR7 to the NK cell response following IAV infection has not been addressed. We have analyzed lung cytokine responses as well as the activation, interferon (IFN)-γ production, and cytotoxicity of lung and splenic NK cells following sublethal respiratory IAV infection in wild-type and TLR7ko mice...
2018: Frontiers in Immunology
Prabuddha S Pathinayake, Alan C-Y Hsu, David W Waters, Philip M Hansbro, Lisa G Wood, Peter A B Wark
Asthma is a heterogeneous, chronic inflammatory disease of the airways. It is a complex disease with different clinical phenotypes and results in a substantial socioeconomic burden globally. Poor understanding of pathogenic mechanisms of the disease hinders the investigation into novel therapeutics. Emerging evidence of the unfolded protein response (UPR) in the endoplasmic reticulum (ER) has demonstrated previously unknown functions of this response in asthma development. A worsening of asthmatic condition can be brought on by stimuli such as oxidative stress, pathogenic infections, and allergen exposure...
2018: Frontiers in Immunology
Kei Yamasaki, Stephan F van Eeden
Lung macrophages (LMs) are essential immune effector cells that are pivotal in both innate and adaptive immune responses to inhaled foreign matter. They either reside within the airways and lung tissues (from early life) or are derived from blood monocytes. Similar to macrophages in other organs and tissues, LMs have natural plasticity and can change phenotype and function depending largely on the microenvironment they reside in. Phenotype changes in lung tissue macrophages have been implicated in chronic inflammatory responses and disease progression of various chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD)...
February 15, 2018: International Journal of Molecular Sciences
Leina B Saito, Laura Diaz-Satizabal, Danyel Evseev, Ximena Fleming-Canepa, Sai Mao, Robert G Webster, Katharine E Magor
Ducks, the reservoir host, are generally permissive to influenza A virus infection without disease symptoms. This natural ecology was upset by the emergence of H5N1 strains, which can kill ducks. To better understand host-virus interactions in the reservoir host, and influenza strain-specific molecular contributions to virulence, we infected White Pekin ducks with three similar H5N1 viruses, with known differences in pathogenicity and replication rate. We quantified viral replication and innate immune gene activation by qPCR, in lung and spleen tissues, isolated on each of the first 3 days of infection...
February 12, 2018: Journal of General Virology
Tsunahiko Hirano, Kazuto Matsunaga
Because the pathophysiology of asthma has diverse characteristics, to manage the disease effectively, it is important for clinicians to distinguish among the clinical phenotypes. Among them, adult-onset asthma, that is, late-onset asthma (LOA), is increasing because of the aging of the population. The phenotype of LOA is largely divided into two types according to the presence or absence of eosinophilic inflammation, T-helper (Th)2- and non-Th2-associated LOA. Especially in Th2 LOA related to rhinosinusitis, as pulmonary function at onset is poor and asthma exacerbations occur frequently, it is important to detect this phenotype in the early phase by using a biomarker of Th2-type inflammation such as fractional exhaled nitric oxide (FE NO )...
2018: Journal of Asthma and Allergy
Dominik Hartl, Rabindra Tirouvanziam, Julie Laval, Catherine M Greene, David Habiel, Lokesh Sharma, Ali Önder Yildirim, Charles S Dela Cruz, Cory M Hogaboam
The respiratory tract is faced daily with 10,000 L of inhaled air. While the majority of air contains harmless environmental components, the pulmonary immune system also has to cope with harmful microbial or sterile threats and react rapidly to protect the host at this intimate barrier zone. The airways are endowed with a broad armamentarium of cellular and humoral host defense mechanisms, most of which belong to the innate arm of the immune system. The complex interplay between resident and infiltrating immune cells and secreted innate immune proteins shapes the outcome of host-pathogen, host-allergen, and host-particle interactions within the mucosal airway compartment...
February 13, 2018: Journal of Innate Immunity
Beata Brajer-Luftmann, Agata Nowicka, Mariusz Kaczmarek, Magdalena Wyrzykiewicz, Senan Yasar, Tomasz Piorunek, Marcin Grabicki, Magdalena Kostrzewska, Jan Sikora, Halina Batura-Gabryel
Chronic exposure to detrimental environmental factors may induce immunogenic cell death of structural airway cells in chronic obstructive pulmonary disease (COPD). Damage-associated molecular patterns (DAMPs) is a family of heterogeneous molecules released from injured or dead cells, which activate innate and adaptive immune responses on binding to the pattern recognition receptors on cells. This study seeks to define the content of DAMPs in the bronchoalveolar lavage fluid (BALF) and serum of COPD patients, and the possible association of these molecules with clinical disease features...
February 11, 2018: Advances in Experimental Medicine and Biology
Yueh-Ying Han, Erick Forno, Nitin Shivappa, Michael D Wirth, James R Hébert, Juan C Celedón
BACKGROUND: A proinflammatory diet may increase allergic airway inflammation by affecting innate and adaptive immune responses. OBJECTIVE: In this study, we examine the relation between the diet's inflammatory potential, measured by the Dietary Inflammatory Index (DII), and current asthma, current wheeze, and lung function in U.S. children and adults. METHODS: We analyzed data from 8,175 children (aged 6-17 years) and 22,294 adults (aged 18-79 years) who participated in the 2007-2012 National Health and Nutrition Examination Survey...
February 6, 2018: Journal of Allergy and Clinical Immunology in Practice
A Kalinowski, B T Galen, I F Ueki, Y Sun, A Mulenos, A Osafo-Addo, B Clark, J Joerns, W Liu, J A Nadel, C S Dela Cruz, J L Koff
Respiratory syncytial virus (RSV) persists as a significant human pathogen that continues to contribute to morbidity and mortality. In children, RSV is the leading cause of lower respiratory tract infections, and in adults RSV causes pneumonia and contributes to exacerbations of chronic lung diseases. RSV induces airway epithelial inflammation by activation of the epidermal growth factor receptor (EGFR), a tyrosine kinase receptor. Recently, EGFR inhibition was shown to decrease RSV infection, but the mechanism(s) for this effect are not known...
February 7, 2018: Mucosal Immunology
Sui-Chu Yin, En-Chih Liao, Chi-Xin Ye, Ching-Yun Chang, Jaw-Ji Tsai
The major mite allergenic components of protease allergens (group 1,3) and non-protease allergens (group 2,7) derived from Dermatophagoides peronyssinus (Dp) and D. farinae (Df) are reported to be capable of sensitizing 80-90% of mite-allergic patients. Although protease and non-protease allergens have been demonstrated to trigger innate and adaptive immune responses through epithelium activation, the simultaneous or sequential effects of both groups of allergens has not been reported. Since all allergens are present in the mite crude extracts, it is important to determine whether these allergens can synergistically trigger the immune responses to cause airway inflammation...
October 26, 2017: Immunobiology
Wael Alturaiki, Amanda J McFarlane, Katie Rose, Rachel Corkhill, Paul S McNamara, Jürgen Schwarze, Brian F Flanagan
Innate immune responses are known to influence the subsequent development of adaptive immunity. We have previously shown that RSV infection of human airway epithelial cells results in production of the B cell growth factor, BAFF. To better understand how the airway responds to RSV infection by production of this and other factors to support or enhance local B cell responses to infection, we analysed the lung expression of BAFF and B cell homeostatic chemokines CXCL12, CXCL13, CCL19 and CCL21 in a murine model of RSV infection...
January 26, 2018: Cytokine
Nithyananda Thorenoor, Xuesheng Zhang, Todd M Umstead, E Scott Halstead, David S Phelps, Joanna Floros
BACKGROUND: Surfactant Protein-A (SP-A) is a major protein component of surfactant and plays a role in surfactant-related functions and innate immunity. Human SP-A consists of two functional genes, SFTPA1 and SFTPA2, encoding SP-A1 and SP-A2 proteins, respectively and each is identified with numerous genetic variants. These differentially enhance bacterial phagocytosis, with SP-A2 variants being more effective than SP-A1. METHODS: Lung functions of humanized transgenic (hTG) mice that carry different SP-A1 and SP-A2 variants or both variants SP-A1/SP-A2 (6A2/1A0, co-ex), as well as SP-A knockout (KO), were studied...
February 3, 2018: Respiratory Research
Koichi Hirose, Takashi Ito, Hiroshi Nakajima
Asthma is a chronic inflammatory disease of the airways that is characterized by eosinophilic inflammation, mucus hypersecretion and airway remodeling that leads to airway obstruction. Although these pathognomonic features of asthma are primarily mediated by allergen-specific T helper type 2 cells (Th2 cells) and their cytokines, recent studies have revealed critical roles of lung epithelial cells in the pathogenesis of asthma. Lung epithelial cells not only form physical barriers by covering the surfaces of the airways but also sense inhaled allergens and initiate communication between the environment and the immune system...
January 31, 2018: International Immunology
Marcin Kurowski, Janusz Jurczyk, Sylwia Moskwa, Marzanna Jarzębska, Hubert Krysztofiak, Marek L Kowalski
Introduction: Regular training modulates airway inflammation and modifies susceptibility to respiratory infections. The impact of exercise and ambient conditions on airway hyperreactivity and innate immunity has not been well studied. We aimed to assess exercise-related symptoms, lung function, airway hyperresponsiveness and innate immunity proteins in relation to meteorological conditions and exercise load in competitive athletes. Material and methods: Thirty-six speed skaters were assessed during winter (WTP) and summer (STP) periods...
January 2018: Archives of Medical Science: AMS
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