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Airway innate immunity

Jennifer H Madenspacher, Michael B Fessler
Although community-acquired pneumonia remains a major public health problem, murine models of bacterial pneumonia have recently facilitated significant preclinical advances in our understanding of the underlying cellular and molecular pathogenesis. In vivo mouse models capture the integrated physiology and resilience of the host defense response in a manner not revealed by alternative, simplified ex vivo approaches. Several methods have been described in the literature for intrapulmonary inoculation of bacteria in mice, including aerosolization, intranasal delivery, peroral endotracheal cannulation under 'blind' and visualized conditions, and transcutaneous endotracheal cannulation...
September 28, 2016: Journal of Visualized Experiments: JoVE
Christine M Freeman, Jeffrey L Curtis
Hallmarks of chronic obstructive pulmonary disease (COPD) include innate inflammation and remodeling of small airways that begin in early disease and the development of lung lymphoid follicles (LLF), indicative of adaptive immunity, in more spirometrically-severe stages. Common to these processes in all stages is orchestration by dendritic cells (DC). Recently improved understanding of the analogous lung DC subsets in humans and mice has allowed for better integration and interpretation of the experimental and clinical pathological literature...
October 21, 2016: American Journal of Respiratory Cell and Molecular Biology
Hitendra S Chand, Yohannes A Mebratu, Marena Montera, Yohannes Tesfaigzi
BACKGROUND: Airway epithelial cells (AECs) are crucial for mucosal and adaptive immunity but whether these cells respond in a memory-dependent manner is poorly studied. Previously, we have reported that LPS intratracheal instillation in rodents causes extensive neutrophilic inflammation and airway epithelial cell hyperplasia accompanied by mucous cell metaplasia (MCM). And the resolution process required a period of 40 d for the inflammation to subside and the lung epithelia to resemble the non-exposed condition...
October 20, 2016: Respiratory Research
Fahima Madouri, Pauline Chenuet, Chloé Beuraud, Louis Fauconnier, Tiffany Marchiol, Nathalie Rouxel, Aurélie Ledru, Margaux Gallerand, Vincent Lombardi, Laurent Mascarell, Quentin Marquant, Lionel Apetoh, François Erard, Marc Le Bert, Fabrice Trovero, Valérie F J Quesniaux, Bernhard Ryffel, Dieudonnée Togbe
BACKGROUND: Protein Kinase C theta (PKC-θ), a serine/threonine kinase is involved in T helper 2 (Th2) cell activation and proliferation. Innate lymphoid cells 2 (ILC2) resemble Th2 cells; produce the Th2 cytokines IL-5 and IL-13, but lack antigen specific receptors. The mechanism by which PKC-θ drives innate immune cells to instruct Th2 responses in allergic lung inflammation remains unknown. OBJECTIVES: We hypothesized that PKC-θ contributes to ILC2 activation and may be necessary for ILC2 to instruct Th2 response...
October 13, 2016: Journal of Allergy and Clinical Immunology
Kazuya Shirato, Kazuhiko Kanou, Miyuki Kawase, Shutoku Matsuyama
: Human coronavirus 229E (HCoV-229E), a causative agent of the common cold, enters host cells via two distinct pathways: one is mediated by cell surface proteases, particularly transmembrane protease serine 2 (TMPRSS2), and the other by endosomal cathepsin L. Thus, specific inhibitors of these proteases block virus infection. However, it is unclear which of these pathways is actually utilized by HCoV-229E in the human respiratory tract. Here, we examined the mechanism of cell entry used by a pseudotyped virus bearing the HCoV-229E spike (S) protein in the presence/absence of protease inhibitors...
October 12, 2016: Journal of Virology
Erik Tenland, Gisela Håkansson, Nader Alaridah, Nataliya Lutay, Anna Rönnholm, Oskar Hallgren, Gunilla Westergren-Thorsson, Gabriela Godaly
Mycobacterium bovis bacilli Calmette-Guerin (BCG) is used as a benchmark to compare the immunogenicity of new vaccines against tuberculosis. This live vaccine is administered intradermal, but several new studies show that changing the route to mucosal immunisation represents an improved strategy. We analysed the immunomodulatory functions of BCG on human neutrophils and primary airway epithelial cells (AECs), as the early events of mucosal immune activation are unclear. Neutrophils and the primary epithelial cells were found to express the IL-17A receptor subunit IL-17RA, while the expression of IL-17RE was only observed on epithelial cells...
2016: PloS One
Engin Baturcam, Natale Snape, Tiong Han Yeo, Johanna Schagen, Emma Thomas, Jayden Logan, Sally Galbraith, Natasha Collinson, Simon Phipps, Emmanuelle Fantino, Peter D Sly, Kirsten M Spann
Asthmatics are highly susceptible to respiratory viral infections, possibly due to impaired innate immunity. However, the exact mechanisms of susceptibility are likely to differ amongst viruses. Therefore, we infected primary nasal epithelial cells (NECs) from adults with mild-to-moderate asthma, with respiratory syncytial virus (RSV) or human metapneumovirus (hMPV) in vitro and investigated the antiviral response. NECs from these asthmatics supported elevated hMPV but not RSV infection, compared to non-asthmatic controls...
October 11, 2016: Journal of Innate Immunity
Diamanda Rigas, Gavin Lewis, Jennifer L Aron, Bowen Wang, Homayon Banie, Ishwarya Sankaranarayanan, Lauriane Galle-Treger, Hadi Maazi, Richard Lo, Gordon J Freeman, Arlene H Sharpe, Pejman Soroosh, Omid Akbari
BACKGROUND: Atopic diseases including asthma exacerbate type 2 immune responses and involve a number of immune cell types, including regulatory T cells (Tregs) and the emerging group 2 innate lymphoid cells (ILC2s). While ILC2s are potent producers of type 2 cytokines, the regulation of ILC2 activation and function is not well understood. OBJECTIVE: In the present study, we evaluate for the first time how Tregs interact with pulmonary ILC2s and control their function...
October 4, 2016: Journal of Allergy and Clinical Immunology
Mihnea T Zdrenghea, Heidi Makrinioti, Cristina Bagacean, Andy Bush, Sebastian L Johnston, Luminita A Stanciu
Vitamin D, in addition to its classical functions in bone homeostasis, has a modulatory and regulatory role in multiple processes, including host defense, inflammation, immunity, and epithelial repair. Patients with respiratory disease are frequently deficient in vitamin D, implying that supplementation might provide significant benefit to these patients. Respiratory viral infections are common and are the main trigger of acute exacerbations and hospitalization in children and adults with asthma and other airways diseases...
October 7, 2016: Reviews in Medical Virology
Josalyn L Cho, Morris F Ling, David C Adams, Lucas Faustino, Sabina A Islam, Roshi Afshar, Jason W Griffith, Robert S Harris, Aylwin Ng, Giorgia Radicioni, Amina A Ford, Andre K Han, Ramnik Xavier, William W Kwok, Richard Boucher, James J Moon, Daniel L Hamilos, Mehmet Kesimer, Melissa J Suter, Benjamin D Medoff, Andrew D Luster
Despite systemic sensitization, not all allergic individuals develop asthma symptoms upon airborne allergen exposure. Determination of the factors that lead to the asthma phenotype in allergic individuals could guide treatment and identify novel therapeutic targets. We used segmental allergen challenge of allergic asthmatics (AA) and allergic nonasthmatic controls (AC) to determine whether there are differences in the airway immune response or airway structural cells that could drive the development of asthma...
October 5, 2016: Science Translational Medicine
Anders Andersson, Carina Malmhäll, Birgitta Houltz, Sara Tengvall, Margareta Sjöstrand, Ingemar Qvarfordt, Anders Lindén, Apostolos Bossios
BACKGROUND: Long-term exposure to tobacco smoke causes local inflammation in the airways that involves not only innate immune cells, including NK cells, but also adaptive immune cells such as cytotoxic (CD8(+)) and helper (CD4(+)) T-cells. We have previously demonstrated that long-term tobacco smoking increases extracellular concentration of the CD4(+)-recruiting cytokine interleukin (IL)-16 locally in the airways. Here, we hypothesized that tobacco smoking alters IL-16 biology at the systemic level and that this effect involves oxygen free radicals (OFR)...
2016: International Journal of Chronic Obstructive Pulmonary Disease
Mingyuan Han, Jun Young Hong, Suraj Jaipalli, Charu Rajput, Jing Lei, Joanna L Hinde, Qiang Chen, Natalie M Hershenson, J Kelley Bentley, Marc B Hershenson
Early-life wheezing-associated infections with rhinovirus (RV) have been associated with asthma development in children. We have shown that RV infection of six day-old mice induces mucous metaplasia and airways hyperresponsiveness which is dependent on IL-13, IL-25 and type 2 innate lymphoid cells (ILC2s). Infection of immature mice fails to induce lung IFN-γ expression, in contrast to mature 8 week-old mice with a robust IFN-γ response, consistent with the notion that deficient IFN-γ production in immature mice permits RV-induced type 2 immune responses...
September 28, 2016: American Journal of Respiratory Cell and Molecular Biology
Andriana I Papaioannou, Aris Spathis, Konstantinos Kostikas, Petros Karakitsos, Spyros Papiris, Christos Rossios
Asthma is a heterogeneous inflammatory disease caused by association of genetic and environmental factors and its incidence has significantly increased over the latest years. The clinical manifestations of asthma are the result of airway hyper-reactivity to a variety of triggers such as aeroallergens, viral and bacterial components. Toll-like receptors (TLRs) are pathogen associated molecular pattern receptors, which are also expressed in the lung tissue as well as in several cells of the innate and adaptive immune system...
September 24, 2016: European Journal of Pharmacology
Ayako Matsuki, Hiroaki Takatori, Sohei Makita, Masaya Yokota, Tomohiro Tamachi, Akira Suto, Kotaro Suzuki, Koichi Hirose, Hiroshi Nakajima
BACKGROUND: Innate lymphoid cells (ILCs) are emerging subsets of immune cells that produce large amounts of cytokines upon cytokine and/or alarmin stimulation. Recent studies have shown that T-bet plays pivotal roles in the development of ILC3s and ILC1s; however, the roles of T-bet in lung ILC2s remain unknown. OBJECTIVE: To determine the role of T-bet in ILC2-mediated airway inflammation. METHODS: The expression of T-bet in lung ILCs (defined as Thy1...
September 23, 2016: Journal of Allergy and Clinical Immunology
Erika Simmerman, Xu Qin, Brendan Marshall, Libby Perry, Lei Cai, Tailing Wang, Jack Yu, Omid Akbari, Babak Baban
BACKGROUND: Cleft lip and palate reconstructions demonstrate significantly lower surgical site infection rates compared with clean-contaminated cases, prompting investigation into the pathophysiology causing this discrepancy. Recent studies have identified a new group of innate lymphocytes called innate lymphoid cells (ILCs), located in barrier surfaces of the skin, airways, and intestine. Our objectives were to explore for the first time the presence of ILCs in the vermillion of neonates and young children undergoing cleft lip reconstruction and characterize their composition by measuring the three classes of ILCs...
October 2016: Journal of Surgical Research
Noam A Cohen
OBJECTIVE: Chronic rhinosinusitis (CRS) refractory to therapeutic intervention may involve a particularly resistant infection known as a bacterial biofilm. Critical to biofilm formation is the microbial process of quorum sensing whereby microbes secrete factors that regulate the expression of microbial genes involved in biofilm formation, persistence, and virulence. Here, we review recent work demonstrating that the bitter taste receptor T2R38, expressed on the apical surface of the sinonasal epithelium, serves a sentinel role in eavesdropping on microbial quorum-sensing communications and regulates localized innate biocidal defenses...
September 21, 2016: Laryngoscope
Mutlay Sayan, Brooke T Mossman
The concept of the inflammasome, a macromolecular complex sensing cell stress or danger signals and initiating inflammation, was first introduced approximately a decade ago. Priming and activation of these intracellular protein platforms trigger the maturation of pro-inflammatory chemokines and cytokines, most notably, interleukin-1β (IL-1β) and IL-18, to promulgate innate immune defenses. Although classically studied in models of gout, Type II diabetes, Alzheimer's disease, and multiple sclerosis, the importance and mechanisms of action of inflammasome priming and activation have recently been elucidated in cells of the respiratory tract where they modulate the responses to a number of inhaled pathogenic particles and fibres...
2016: Particle and Fibre Toxicology
Elizabeth E Cottrill, Bei Chen, Nithin D Adappa, James N Palmer, David W Kennedy, Robert J Lee, Noam A Cohen
BACKGROUND: Antimicrobial peptides (AMPs) produced by the epithelium are important for innate immune defense. In 2001, a novel AMP dermcidin (DCD) was described with no homology to other AMPs and an expression pattern restricted to eccrine sweat glands. In contrast to other AMPs, DCD expression has not been shown to be induced under inflammatory conditions in the skin. After identifying DCD by mass spectrometry in a protein sample isolated from human nasal secretions, we sought to determine the role of DCD in innate defense of the sinonasal airway...
September 21, 2016: International Forum of Allergy & Rhinology
Maria J Gutierrez, Jose L Gomez, Geovanny F Perez, Krishna Pancham, Stephanie Val, Dinesh K Pillai, Mamta Giri, Sarah Ferrante, Robert Freishtat, Mary C Rose, Diego Preciado, Gustavo Nino
BACKGROUND: Innate immune responses are fine-tuned by small noncoding RNA molecules termed microRNAs (miRs) that modify gene expression in response to the environment. During acute infections, miRs can be secreted in extracellular vesicles (EV) to facilitate cell-to-cell genetic communication. The purpose of this study was to characterize the baseline population of miRs secreted in EVs in the airways of young children (airway secretory microRNAome) and examine the changes during rhinovirus (RV) infection, the most common cause of asthma exacerbations and the most important early risk factor for the development of asthma beyond childhood...
2016: PloS One
Ellen L Burnham, Alicia McNally, Jeanette Gaydos, Lou Ann S Brown
BACKGROUND: Alcohol use disorders (AUDs) and cigarette smoking are associated with pulmonary oxidative stress, likely related to antioxidant depletion. Pulmonary oxidative stress may adversely affect innate immunity, leading to increased pneumonia susceptibility and severity, including development of the acute respiratory distress syndrome. In people with AUDs, most of whom smoke, antioxidant therapy can potentially restore immune cell function and attenuate pneumonia development. Challenges to human investigations of antioxidant therapies include an inability to identify pulmonary oxidative stress noninvasively and the optimal route to deliver pulmonary antioxidants...
October 2016: Alcoholism, Clinical and Experimental Research
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