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Airway innate immunity

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https://www.readbyqxmd.com/read/28729052/tedizolid-inhibits-muc5ac-production-induced-by-methicillin-resistant-staphylococcus-aureus-in-human-airway-epithelial-cells
#1
Kazuaki Takeda, Norihito Kaku, Yoshitomo Morinaga, Kosuke Kosai, Naoki Uno, Yoshifumi Imamura, Hiroo Hasegawa, Taiga Miyazaki, Koichi Izumikawa, Hiroshi Mukae, Katsunori Yanagihara
The innate immune system plays an important role in early immunity against respiratory tract infection. Although airway epithelial cells produce mucus to eliminate pathogens and irritants, hypersecretion of mucus is harmful for the host as it may cause airway obstruction and inhibit influx of antimicrobial agents. It has been reported that several antimicrobial agents have an immunomodulatory effect in vitro and in vivo, but little is known about whether tedizolid, a novel oxazolidinone, can modulate immune responses...
July 17, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28727907/novel-role-of-surfactant-protein-a-in-bacterial-sinusitis
#2
George T Noutsios, Amanda L Willis, Julie G Ledford, Eugene H Chang
BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disorder of the upper airway characterized by chronic inflammation and significant sinonasal remodeling. CRS is comprised of 2 major subgroups, based on whether polyps are present or absent. In some cases, it is characterized by colonization with opportunistic pathogens such as Pseudomonas aeruginosa (PA), Staphylococcus aureus, and other bacteria. The innate immune system of the sinonasal epithelium is the first line of defense against inhaled pathogens...
July 20, 2017: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/28713772/harnessing-neutrophil-survival-mechanisms-during-chronic-infection-by-pseudomonas-aeruginosa-novel-therapeutic-targets-to-dampen-inflammation-in-cystic-fibrosis
#3
REVIEW
Benoît S Marteyn, Pierre-Régis Burgel, Laurent Meijer, Véronique Witko-Sarsat
More than two decades after cloning the cystic fibrosis transmembrane regulator (CFTR) gene, the defective gene in cystic fibrosis (CF), we still do not understand how dysfunction of this ion channel causes lung disease and the tremendous neutrophil burden which persists within the airways; nor why chronic colonization by Pseudomonas aeruginosa develops in CF patients who are thought to be immunocompetent. It appears that the microenvironment within the lung of CF patients provides favorable conditions for both P...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28705588/elevated-uric-acid-and-adenosine-triphosphate-concentrations-in-bronchoalveolar-lavage-fluid-of-eosinophilic-pneumonia
#4
Takehito Kobayashi, Kazuyuki Nakagome, Toru Noguchi, Kiyoko Kobayashi, Yutaka Ueda, Tomoyuki Soma, Kenji Ikebuchi, Hidetomo Nakamoto, Makoto Nagata
BACKGROUND: Recent evidence has suggested that the innate immune response may play a role in the development of eosinophilic airway inflammation. We previously reported that uric acid (UA) and adenosine triphosphate (ATP), two important damage-associated molecular pattern molecules (DAMPs), activate eosinophil functions, suggesting that these molecules may be involved in the development of eosinophilic airway inflammation. The objective of this study was to measure the concentrations of DAMPs including UA and ATP in the bronchoalveolar lavage fluid (BALF) of patients with eosinophilic pneumonia (EP)...
July 10, 2017: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/28684799/modifications-of-pseudomonas-aeruginosa-cell-envelope-in-the-cystic-fibrosis-airway-alters-interactions-with-immune-cells
#5
Preston J Hill, Julia M Scordo, Jesús Arcos, Stephen E Kirkby, Mark D Wewers, Daniel J Wozniak, Jordi B Torrelles
Pseudomonas aeruginosa is a ubiquitous environmental organism and an opportunistic pathogen that causes chronic lung infections in the airways of cystic fibrosis (CF) patients as well as other immune-compromised individuals. During infection, P. aeruginosa enters the terminal bronchioles and alveoli and comes into contact with alveolar lining fluid (ALF), which contains homeostatic and antimicrobial hydrolytic activities, termed hydrolases. These hydrolases comprise an array of lipases, glycosidases, and proteases and thus, they have the potential to modify lipids, carbohydrates and proteins on the surface of invading microbes...
July 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28676074/immunoregulatory-effects-of-multipotent-adult-progenitor-cells-in-a-porcine-ex-vivo-lung-perfusion-model
#6
An Martens, Sofie Ordies, Bart M Vanaudenaerde, Stijn E Verleden, Robin Vos, Dirk E Van Raemdonck, Geert M Verleden, Valerie D Roobrouck, Sandra Claes, Dominique Schols, Eric Verbeken, Catherine M Verfaillie, Arne P Neyrinck
BACKGROUND: Primary graft dysfunction (PGD) is considered to be the end result of an inflammatory response targeting the new lung allograft after transplant. Previous research has indicated that MAPC cell therapy might attenuate this injury by its paracrine effects on the pro-/anti-inflammatory balance. This study aims to investigate the immunoregulatory capacities of MAPC cells in PGD when administered in the airways. METHODS: Lungs of domestic pigs (n = 6/group) were subjected to 90 minutes of warm ischemia...
July 5, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28667163/leukotriene-c4-potentiates-il-33-induced-group-2-innate-lymphoid-cell-activation-and-lung-inflammation
#7
Sean J Lund, Alex Portillo, Kellen Cavagnero, Rachel E Baum, Luay H Naji, Jana H Badrani, Amit Mehta, Michael Croft, David H Broide, Taylor A Doherty
Asthma is a complex disease that is promoted by dysregulated immunity and the presence of many cytokine and lipid mediators. Despite this, there is a paucity of data demonstrating the combined effects of multiple mediators in asthma pathogenesis. Group 2 innate lymphoid cells (ILC2s) have recently been shown to play important roles in the initiation of allergic inflammation; however, it is unclear whether lipid mediators, such as cysteinyl leukotrienes (CysLTs), which are present in asthma, could further amplify the effects of IL-33 on ILC2 activation and lung inflammation...
June 30, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28667161/cd36-and-platelet-activating-factor-receptor-promote-house-dust-mite-allergy-development
#8
Preeyam S Patel, John F Kearney
Over 89% of asthmatic children in underdeveloped countries demonstrate sensitivity to house dust mites (HDMs). The allergic response to HDMs is partially mediated by epithelial cell-derived cytokines that activate group 2 innate lymphoid cells, induce migration and activation of dendritic cells, and promote effector differentiation of HDM-specific TH2 cells. However, the contribution of innate receptor engagement on epithelial or dendritic cells by HDMs that ultimately mediates said innate and adaptive allergic responses is poorly understood...
June 30, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28667160/early-postnatal-secondhand-smoke-exposure-disrupts-bacterial-clearance-and-abolishes-immune-responses-in-muco-obstructive-lung-disease
#9
Brandon W Lewis, Razia Sultana, Rahul Sharma, Alexandra Noël, Ingeborg Langohr, Sonika Patial, Arthur L Penn, Yogesh Saini
Secondhand smoke (SHS) exposure has been linked to the worsening of ongoing lung diseases. However, whether SHS exposure affects the manifestation and natural history of imminent pediatric muco-obstructive airway diseases such as cystic fibrosis remains unclear. To address these questions, we exposed Scnn1b transgenic (Scnn1b-Tg(+)) mice to SHS from postnatal day (PND) 3-21 and lung phenotypes were examined at PND22. Although a majority of filtered air (FA)-exposed Scnn1b-Tg(+) (FA-Tg(+)) mice successfully cleared spontaneous bacterial infections by PND22, the SHS-exposed Scnn1b-Tg(+) (SHS-Tg(+)) mice failed to resolve these infections...
June 30, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28667069/role-of-human-metapneumovirus-and-respiratory-syncytial-virus-in-asthma-exacerbations-where-are-we-now
#10
REVIEW
Penny A Rudd, Belinda J Thomas, Ali Zaid, Martin MacDonald, Keiko Kan-O, Michael S Rolph, Anand R Soorneedi, Philip G Bardin, Suresh Mahalingam
Since its discovery in 2001, human metapneumovirus (hMPV) has been identified as an important cause of respiratory tract infection in young children, second only to the closely related respiratory syncytial virus (RSV). Clinical evidence suggests that hMPV is associated with acute exacerbations of asthma in both children and adults, and may play a role in initiating asthma development in children. Animal models have demonstrated that airway hyperresponsiveness (AHR) and inflammation are triggered following hMPV infection, and hMPV is able to persist in vivo by inhibiting innate immune responses and causing aberrant adaptive responses...
July 15, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28665939/the-rna-uridyltransferase-zcchc6-is-expressed-in-macrophages-and-impacts-innate-immune-responses
#11
Elyse Kozlowski, Gregory A Wasserman, Marcos Morgan, Dónal O'Carroll, Nora-Guadalupe P Ramirez, Suryaram Gummuluru, Jasmine Y Rah, Adam C Gower, Michael Ieong, Lee J Quinton, Joseph P Mizgerd, Matthew R Jones
Alveolar macrophages orchestrate pulmonary innate immunity and are essential for early immune surveillance and clearance of microorganisms in the airways. Inflammatory signaling must be sufficiently robust to promote host defense but limited enough to prevent excessive tissue injury. Macrophages in the lungs utilize multiple transcriptional and post-transcriptional mechanisms of inflammatory gene expression to delicately balance the elaboration of immune mediators. RNA terminal uridyltransferases (TUTs), including the closely homologous family members Zcchc6 (TUT7) and Zcchc11 (TUT4), have been implicated in the post-transcriptional regulation of inflammation from studies conducted in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28658560/il-33-biological-properties-functions-and-roles-in-airway-disease
#12
REVIEW
Li Yin Drake, Hirohito Kita
Interleukin (IL)-33 is a key cytokine involved in type 2 immunity and allergic airway diseases. Abundantly expressed in lung epithelial cells, IL-33 plays critical roles in both innate and adaptive immune responses in mucosal organs. In innate immunity, IL-33 and group 2 innate lymphoid cells (ILC2s) provide an essential axis for rapid immune responses and tissue homeostasis. In adaptive immunity, IL-33 interacts with dendritic cells, Th2 cells, follicular T cells, and regulatory T cells, where IL-33 influences the development of chronic airway inflammation and tissue remodeling...
July 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28658554/are-ilc2s-jekyll-and-hyde-in-airway-inflammation
#13
REVIEW
Kafi N Ealey, Kazuyo Moro, Shigeo Koyasu
Asthma is a complex heterogeneous disease of the airways characterized by lung inflammation, airway hyperreactivity (AHR), mucus overproduction, and remodeling of the airways. Group 2 innate lymphoid cells (ILC2s) play a crucial role in the initiation and propagation of type 2 inflammatory programs in allergic asthma models, independent of adaptive immunity. In response to allergen, helminths or viral infection, damaged airway epithelial cells secrete IL-33, IL-25, and thymic stromal lymphopoietin (TSLP), which activate ILC2s to produce type 2 cytokines such as IL-5, IL-13, and IL-9...
July 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28658543/modeling-th-2-responses-and-airway-inflammation-to-understand-fundamental-mechanisms-regulating-the-pathogenesis-of-asthma
#14
REVIEW
Paul S Foster, Steven Maltby, Helene F Rosenberg, Hock L Tay, Simon P Hogan, Adam M Collison, Ming Yang, Gerard E Kaiko, Philip M Hansbro, Rakesh K Kumar, Joerg Mattes
In this review, we highlight experiments conducted in our laboratories that have elucidated functional roles for CD4(+) T-helper type-2 lymphocytes (TH 2 cells), their associated cytokines, and eosinophils in the regulation of hallmark features of allergic asthma. Notably, we consider the complexity of type-2 responses and studies that have explored integrated signaling among classical TH 2 cytokines (IL-4, IL-5, and IL-13), which together with CCL11 (eotaxin-1) regulate critical aspects of eosinophil recruitment, allergic inflammation, and airway hyper-responsiveness (AHR)...
July 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28650258/helper-t-cell-responses-to-respiratory-viruses-in-the-lung-development-virus-suppression-and-pathogenesis
#15
Kosuke Miyauchi
The lung is an important line of defense that is exposed to respiratory infectious pathogens, including viruses. Lung epithelial cells and/or alveolar macrophages are initially targeted by respiratory viruses. Once respiratory viruses invade the cells of the lung, innate immunity is activated to inhibit viral replication. Innate immune signaling also activates virus-specific adaptive immune responses. The helper T cells play pivotal roles in the humoral and cellular adaptive immune responses. Helper T cells are categorized into several distinct subsets (e...
July 2017: Viral Immunology
https://www.readbyqxmd.com/read/28626064/monitoring-c3ar-expression-using-a-floxed-tdtomato-c3ar-reporter-knock-in-mouse
#16
Katharina M Quell, Christian M Karsten, Anna Kordowski, Larissa Nogueira Almeida, Daria Briukhovetska, Anna V Wiese, Jing Sun, Fanny Ender, Konstantina Antoniou, Torsten Schröder, Inken Schmudde, Johann L Berger, Peter König, Tillman Vollbrandt, Yves Laumonnier, Jörg Köhl
C3a exerts multiple biologic functions through activation of its cognate C3a receptor. C3(-/-) and C3aR(-/-) mice have been instrumental in defining important roles of the C3a/C3aR axis in the regulation of acute and chronic inflammatory diseases, including ischemia/reperfusion injury, allergic asthma, autoimmune nephritis, and rheumatoid arthritis. Surprisingly little is known about C3aR expression and function in immune and stromal cells. To close this gap, we generated a floxed tandem-dye Tomato (tdTomato)-C3aR reporter knock-in mouse, which we used to monitor C3aR expression in cells residing in the lung, airways, lamina propria (LP) of the small intestine, brain, visceral adipose tissue, bone marrow (BM), spleen, and the circulation...
June 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28625800/arsenic-alters-transcriptional-responses-to-pseudomonas-aeruginosa-infection-and-decreases-antimicrobial-defense-of-human-airway-epithelial-cells
#17
Britton C Goodale, Erica J Rayack, Bruce A Stanton
Arsenic contamination of drinking water and food threatens the health of hundreds of millions of people worldwide by increasing the risk of numerous diseases. Arsenic exposure has been associated with infectious lung disease in epidemiological studies, but it is not yet understood how ingestion of low levels of arsenic increases susceptibility to bacterial infection. Accordingly, the goal of this study was to examine the effect of arsenic on gene expression in primary human bronchial epithelial (HBE) cells and to determine if arsenic altered epithelial cell responses to Pseudomonas aeruginosa, an opportunistic pathogen...
June 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28605742/endotoxin-exposure-increases-ll-37-but-not-calprotectin-in-healthy-human-airways
#18
Margaretha E Smith, Marit Stockfelt, Sara Tengvall, Peter Bergman, Anders Lindén, Ingemar Qvarfordt
RATIONALE: The antimicrobial peptides (AMPs) LL-37 and calprotectin are important players in the innate immunity of human airways. In patients with diseases characterized by bacterial colonization, the airway concentrations of these AMPs are increased. Less is known about their presence and release patterns in healthy humans. Our aim was to determine whether LL-37 and calprotectin are released after the activation of the innate immune response in the peripheral airways. METHODS: Healthy volunteers underwent exposure to endotoxin and vehicle in contralateral segment bronchi...
June 13, 2017: Journal of Innate Immunity
https://www.readbyqxmd.com/read/28601554/eosinophils-in-copd-just-another-biomarker
#19
REVIEW
Mona Bafadhel, Ian D Pavord, Richard E K Russell
Eosinophils are innate immune cells that, under certain conditions, can be recruited to the lungs, where they have an incompletely understood role in health and disease. Eosinophils have been found in the airways, tissues, and circulation of patients with COPD, during both stable disease and exacerbations. Epidemiological studies and post-hoc analyses of clinical trials of corticosteroid treatment for COPD have shown that the blood eosinophil count is associated with the risk of COPD exacerbations, mortality, decline in FEV1, and response to both inhaled and systemic corticosteroids...
June 7, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28583618/new-anti-eosinophil-drugs-for-asthma-and-copd-targeting-the-trait
#20
REVIEW
Elisabeth H Bel, Anneke Ten Brinke
Asthma and chronic obstructive airways disease (COPD) are prevalent chronic inflammatory airway diseases that are responsible for a large global disease burden. Both diseases are complex and heterogeneous, and are increasingly recognized as overlapping syndromes that may share similar pathophysiologic mechanisms and treatable traits. Eosinophilic airway inflammation is considered the most influential treatable trait of chronic airway disease, and over the last decade several monoclonal antibodies and small molecule therapies have been developed to target this trait...
June 2, 2017: Chest
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