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Airway innate immunity

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https://www.readbyqxmd.com/read/28626064/monitoring-c3ar-expression-using-a-floxed-tdtomato-c3ar-reporter-knock-in-mouse
#1
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
#2
B C Goodale, E J Rayack, B 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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28579374/activated-plasmacytoid-dendritic-cells-regulate-type-2-innate-lymphoid-cells-mediated-airway-hyperreactivity
#6
Hadi Maazi, Homayon Banie, German Aleman, Nisheel Patel, Bowen Wang, Ishwarya Sankaranarayanan, Vipul Bhargava, Takahiro Sato, Gavin Lewis, Matteo Cesaroni, James Karras, Anuk Das, Pejman Soroosh, Omid Akbari
BACKGROUND: Allergic asthma is a prevalent inflammatory disease of the airways caused by dysregulated immune balance in the lungs with incompletely understood pathogenesis. The recently identified type 2 innate lymphoid cells (ILC2s) play significant roles in the pathogenesis of asthma. While ILC2-activating factors have been identified, the mechanisms that suppress ILC2s remain largely unknown. Plasmacytoid dendritic cells, pDCs, are important in antiviral immunity and in maintaining tolerance to inert antigens...
June 1, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28576586/-the-lung-microbiota-review
#7
M-C Ploton, S Abakka, E Amouyal, C Besnard, L Dufour, S El Harrif, C Kipnis, B Prim, J Vignot, V Houdouin
In the last 20years, culture-independent DNA-based techniques ("shotgun sequencing") demonstrated that complex microbial communities reside on most epithelial surfaces, including the lower airways. Until the amniotic sac ruptures, a fetus is considered to be essentially sterile. Many factors affect the composition of the lung microbiota: inheritance, mode of delivery, diet, and age-related changes in adults. It interacts with the digestive and oropharyngeal microbiotas. Animal models show that these interactions play a role in innate pulmonary immunity and modulation of the inflammatory response...
May 30, 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/28555513/high-mobility-group-box-protein-1-expression-in-inflammatory-diseases-of-the-middle-ear
#8
Luisa Maria Bellussi, Carla Vindigni, Serena Cocca, Marie Aimee Gloria Munezero Butorano, Walter Livi, Giulia Corallo, Desiderio Passali
High-mobility group box 1 (HMGB1) is a nuclear non-histone protein, playing a critical role as a mediator between innate and acquired immunity; when released extracellularly, it coordinates the cellular stress response (under necrosis, bacterial lipopolysaccharide stimulation) and acts as an inflammatory marker and cytokine. The aim of the study was to demonstrate whether HMGB1 is over-expressed in chronic middle-ear pathologies and whether the entity of expression and the localization are correlated with the degree of the inflammatory reaction, thus suggesting that HMGB1 may play a crucial role in chronic inflammatory disorders of the middle ear, as already demonstrated in other airway diseases...
March 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/28552410/lung-eosinophil-recruitment-in-response-to-aspergillus-fumigatus-is-correlated-with-fungal-cell-wall-composition-and-requires-%C3%AE-%C3%AE-t-cells
#9
Nansalmaa Amarsaikhan, Evan M O'Dea, Angar Tsoggerel, Steven P Templeton
The differential recognition of fungal cell wall polysaccharides that program innate and adaptive immunity to the human opportunistic fungal pathogen Aspergillus fumigatus has been a focus of considerable interest. In a mouse model of fungal conidia aspiration, decreased relative levels of cell wall core carbohydrates β-1,3-glucan to chitin in A. fumigatus isolates and mutant strains were correlated with increased airway eosinophil recruitment. In addition, an increase in fungal surface chitin exposure induced by the β-1,3-glucan synthesis-targeting drug caspofungin was associated with increased murine airway eosinophil recruitment after a single challenge of conidia...
May 25, 2017: Microbes and Infection
https://www.readbyqxmd.com/read/28544570/relative-susceptibility-of-airway-organisms-to-antimicrobial-effects-of-nitric-oxide
#10
Alan D Workman, Ryan M Carey, Michael A Kohanski, David W Kennedy, James N Palmer, Nithin D Adappa, Noam A Cohen
BACKGROUND: Nitric oxide (NO) is released in the airway as a critical component of innate immune defense against invading pathogenic organisms. It is well documented that bacteriostatic and bactericidal effects of NO are concentration-dependent. However, few data exist comparing relative susceptibility of common pathogens to NO at physiologic concentrations. In this study we evaluated the effects of NO on 4 common airway bacteria and 1 fungus, and examined the potential implications of discrepancies in sensitivity...
May 25, 2017: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/28544530/denatonium-induced-sinonasal-bacterial-killing-may-play-a-role-in-chronic-rhinosinusitis-outcomes
#11
Ryan M Carey, Alan D Workman, Kyle M Hatten, Adam P Siebert, Steven G Brooks, Bei Chen, Nithin D Adappa, James N Palmer, David W Kennedy, Robert J Lee, Noam A Cohen
BACKGROUND: Sinonasal bitter taste receptors (T2Rs) contribute to upper airway innate immunity and correlate with chronic rhinosinusitis (CRS) clinical outcomes. A subset of T2Rs expressed on sinonasal solitary chemosensory cells (SCCs) are activated by denatonium, resulting in a calcium-mediated secretion of bactericidal antimicrobial peptides (AMPs) in neighboring ciliated epithelial cells. We hypothesized that there is patient variability in the amount of bacterial killing induced by different concentrations of denatonium and that the differences correlate with CRS clinical outcomes...
May 23, 2017: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/28539439/contribution-of-human-lung-parenchyma-and-leukocyte-influx-to-oxidative-stress-and-immune-mediated-pathology-following-nipah-infection
#12
Olivier Escaffre, Tais B Saito, Terry L Juelich, Tetsuro Ikegami, Jennifer K Smith, David D Perez, Colm Atkins, Corri B Levine, Matthew B Huante, Rebecca J Nusbaum, Janice J Endsley, Alexander N Freiberg, Barry Rockx
Nipah virus (NiV) is a zoonotic emerging paramyxovirus that can cause a fatal respiratory illness or encephalitis in humans. Despite many efforts, the molecular mechanisms of NiV-induced acute lung injury (ALI) remain unclear. We previously showed that NiV replicates to high titers in human lung grafts in NOD scid gamma mice, resulting in a robust inflammatory response. Interestingly, these mice can undergo human immune system reconstitution by the Bone marrow, Liver, and Thymus (BLT) reconstitution method, in addition to lung tissue engraftment, giving altogether a realistic model to study human respiratory viral infections...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28507954/with-friends-like-these-the-complex-role-of-neutrophils-in-the-progression-of-severe-pneumonia
#13
REVIEW
Roger D Pechous
Pneumonia is a leading cause of death from infection in the United States and across the globe. During pulmonary infection, clear resolution of host inflammatory responses occurs in the absence of appreciable lung damage. Neutrophils are the first wave of leukocytes to arrive in the lung upon infection. After activation, neutrophils traffic from the vasculature via transendothelial migration through the lung interstitium and into the alveolar space. Successful pulmonary immunity requires neutrophil-mediated killing of invading pathogens by phagocytosis and release of a myriad of antimicrobial molecules, followed by resolution of inflammation, neutrophil apoptosis, and clearing of dead or dying neutrophils by macrophages...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28502841/use-of-airway-epithelial-cell-culture-to-unravel-the-pathogenesis-and-study-treatment-in-obstructive-airway-diseases
#14
REVIEW
Tinne C J Mertens, Harry Karmouty-Quintana, Christian Taube, Pieter S Hiemstra
Asthma and chronic obstructive pulmonary disease (COPD) are considered as two distinct obstructive diseases. Both chronic diseases share a component of airway epithelial dysfunction. The airway epithelium is localized to deal with inhaled substances, and functions as a barrier preventing penetration of such substances into the body. In addition, the epithelium is involved in the regulation of both innate and adaptive immune responses following inhalation of particles, allergens and pathogens. Through triggering and inducing immune responses, airway epithelial cells contribute to the pathogenesis of both asthma and COPD...
May 11, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28479600/a-crucial-role-of-the-pd-1h-coinhibitory-receptor-in-suppressing-experimental-asthma
#15
Huafeng Liu, Xin Li, Li Hu, Min Zhu, Bailin He, Liqun Luo, Lieping Chen
Programmed death one homolog (PD-1H) is a cell surface molecule of the B7/CD28 immune modulatory gene family. Although PD-1H has been shown to function as a coinhibitory receptor on T cells to limit naive T-cell activation and proliferation, its role in the regulation of the T-cell response to allergens is unknown. We report here that genetic ablation or blockade of PD-1H drastically promotes pulmonary inflammation with massive accumulation of eosinophils in a mouse model of experimental asthma, indicating a suppressive function of PD-1H in allergic inflammation...
May 8, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28474501/pol7085-or-anti-ccl28-treatment-inhibits-development-of-post-paramyxoviral-airway-disease
#16
Becky J Buelow, Michelle Rohlfing, Françoise Jung, Garry J Douglas, Mitchell H Grayson
INTRODUCTION: Asthma is major health burden throughout the world, and there are no therapies that have been shown to be able to prevent the development of disease. A severe respiratory paramyxoviral infection early in life has been demonstrated to greatly increase the risk of developing asthma. We have a mouse model of a severe respiratory paramyxoviral infection (Sendai virus, SeV) that mimics human disease, and requires early expression of the cytokine CCL28 to drive the development of post-viral airway disease...
June 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28468615/epithelial-ciliated-beating-cells-essential-for-ex-vivo-ali-culture-growth
#17
Delphine Gras, Aurélie Petit, Jérémy Charriot, Lucie Knabe, Khuder Alagha, Anne Sophie Gamez, Céline Garulli, Arnaud Bourdin, Pascal Chanez, Nicolas Molinari, Isabelle Vachier
BACKGROUND: Bronchial epithelium plays a key role in orchestrating innate and adaptive immunity. The fate of ex vivo airway epithelial cultures growing at the air liquid interface (ALI) derived from human endobronchial biopsies or brushings is not easy to predict. Calibrating and differentiating these cells is a long and expensive process requiring rigorous expertise. Pinpointing factors associated with ALI culture success would help researchers gain further insight into epithelial progenitor behavior...
May 3, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28463786/innate-immunity-as-the-orchestrator-of-allergic-airway-inflammation-and-resolution-in-asthma
#18
REVIEW
Despoina Thiriou, Ioannis Morianos, Georgina Xanthou, Konstantinos Samitas
The respiratory system is constantly in direct contact with the environment and, has therefore, developed strong innate and adaptive immune responses to combat pathogens. Unlike adaptive immunity which is mounted later in the course of the immune response and is naive at the outset, innate immunity provides the first line of defense against microbial agents, while also promoting resolution of inflammation. In the airways, innate immune effector cells mainly consist of eosinophils, neutrophils, mast cells, basophils, macrophages/monocytes, dendritic cells and innate lymphoid cells, which attack pathogens directly or indirectly through the release of inflammatory cytokines and antimicrobial peptides, and coordinate T and B cell-mediated adaptive immunity...
April 29, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28459101/innate-immunity-and-chronic-rhinosinusitis-what-we-have-learned-from-animal-models
#19
Nyall R London, Andrew P Lane
OBJECTIVE: Chronic rhinosinusitis (CRS) is a heterogeneous and multifactorial disease characterized by dysregulated inflammation. Abnormalities in innate immune function including sinonasal epithelial cell barrier function, mucociliary clearance, response to pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs), and the contribution of innate immune cells will be highlighted in this review. DATA SOURCES: PubMed literature review...
June 2016: Laryngoscope Investigative Otolaryngology
https://www.readbyqxmd.com/read/28433687/steroid-resistance-of-airway-type-2-innate-lymphoid-cells-from-patients-with-severe-asthma-the-role-of-thymic-stromal-lymphopoietin
#20
Sucai Liu, Mukesh Verma, Lidia Michalec, Weimin Liu, Anand Sripada, Donald Rollins, James Good, Yoko Ito, HongWei Chu, Magdalena M Gorska, Richard J Martin, Rafeul Alam
BACKGROUND: Type 2 innate lymphoid cells (ILC2s) represent an important type 2 immune cell. Glucocorticoid regulation of human ILC2s is largely unknown. OBJECTIVE: We sought to assess steroid resistance of human blood and airway ILC2s from asthmatic patients and to examine its mechanism of induction. METHODS: We studied human blood and lung ILC2s from asthmatic patients and control subjects using flow cytometry and ELISA. RESULTS: Dexamethasone inhibited (P = ...
April 20, 2017: Journal of Allergy and Clinical Immunology
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