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Lung immunology

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https://www.readbyqxmd.com/read/28730933/drug-delivery-to-the-lungs-challenges-and-opportunities
#1
Stephen P Newman
Pulmonary drug delivery is relatively complex because the respiratory tract has evolved defense mechanisms to keep inhaled drug particles out of the lungs and to remove or inactivate them once deposited. In addition to these mechanical, chemical and immunological barriers, pulmonary drug delivery is adversely affected by the behavioral barriers of poor adherence and poor inhaler technique. Strategies to mitigate the effects of these barriers include use of inhaler devices and formulations that deliver drug to the lungs efficiently, appropriate inhaler technique and improved education of patients...
July 2017: Therapeutic Delivery
https://www.readbyqxmd.com/read/28730633/pd-1-expression-on-cd8-t-cells-regulates-their-differentiation-within-lung-allografts-and-is-critical-for-tolerance-induction
#2
T Takahashi, H M Hsiao, S Tanaka, W Li, R Higashikubo, D Scozzi, A Bharat, J H Ritter, A S Krupnick, A E Gelman, D Kreisel
Immunological requirements for rejection and tolerance induction differ between various organs. While memory CD8(+) T cells are considered a barrier to immunosuppression-mediated acceptance of most tissues and organs, tolerance induction after lung transplantation is critically dependent on central memory CD8(+) T lymphocytes. Here we demonstrate that costimulation blockade-mediated tolerance after lung transplantation is dependent on PD-1 expression on CD8(+) T cells. In the absence of PD-1 expression, CD8(+) T cells form prolonged interactions with graft-infiltrating CD11c(+) cells, their differentiation is skewed towards an effector memory phenotype and grafts are rejected acutely...
July 20, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28726085/micrornas-in-mucosal-inflammation
#3
REVIEW
Viola Neudecker, Xiaoyi Yuan, Jessica L Bowser, Holger K Eltzschig
Of the total human body's surface, the majority is internal surface, belonging to the lungs (100 m(2)) and intestinal tract (400 m(2)). In comparison, the external surface area, belonging to the skin, comprises less than 1% (2 m(2)). Continuous exposure of the mucosal surface to external factors (e.g., pathogens, food particles) requires tight regulation to maintain homeostasis. MicroRNAs (miRNAs) have gained noticeable attention as playing important roles in maintaining the steady-state of tissues by modulating immune functions and inflammatory responses...
July 20, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28724384/deficiency-of-pi3-kinase-catalytic-isoforms-p110%C3%AE-and-p110%C3%AE-in-mice-enhances-the-il-17-g-csf-axis-and-induces-neutrophilia
#4
Kirsten Bucher, Fee Schmitt, Benedikt Mothes, Carolin Blumendeller, Daniel Schäll, Roland Piekorz, Emilio Hirsch, Bernd Nürnberg, Sandra Beer-Hammer
BACKGROUND: Phosphoinositide 3-kinase γ (PI3Kγ) and PI3Kδ are second messenger-generating enzymes with key roles in proliferation, differentiation, survival, and function of leukocytes. Deficiency of the catalytic subunits p110γ and p110δ of PI3Kγ and PI3Kδ in p110γ/δ(-/-) mice leads to defective B- and T-cell homeostasis. Here we examined the role of p110γ and p110δ in the homeostasis of neutrophils by analyzing p110γ(-/-), p110δ(-/-) and p110γ/δ(-/-) mice. METHODS: Neutrophils and T cells in leukocyte suspensions from the bone marrow (BM), blood, spleen and lung were analyzed by flow cytometry...
July 19, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28722755/the-potential-of-anti-infectives-and-immunomodulators-as-therapies-for-asthma-and-asthma-exacerbations
#5
Michael R Edwards, Ross P Walton, David J Jackson, Wojciech Feleszko, Chrysanthi Skevaki, Tuomas Jartti, Heidi Makrinoti, Alexandra Nikonova, Igor Shilovskiy, Jurgen Schwarze, Sebastian L Johnston, Musa Khaitov
Asthma is responsible for approximately 25,000 deaths annually in Europe despite available medicines that maintain asthma control and reduce asthma exacerbations. Better treatments are urgently needed for the control of chronic asthma and reduction of asthma exacerbations, the major cause of asthma mortality. Much research spanning >20 years shows a strong association between microorganisms including pathogens in asthma onset, severity and exacerbation, yet with the exception of antibiotics, few treatments are available that specifically target the offending pathogens...
July 19, 2017: Allergy
https://www.readbyqxmd.com/read/28720146/analysis-of-long-term-cd4-cd25highcd127-t-reg-cells-kinetics-in-peripheral-blood-of-lung-transplant-recipients
#6
Davide Piloni, Monica Morosini, Sara Magni, Alice Balderacchi, Luigia Scudeller, Emanuela Cova, Tiberio Oggionni, Giulia Stella, Carmine Tinelli, Filippo Antonacci, Andrea Maria D'Armini, Federica Meloni
BACKGROUND: The role of CD4(+)CD25(high)CD127(-) T-reg cells in solid-organ Transplant (Tx) acceptance has been extensively studied. In previous studies on kidney and liver recipients, peripheral T-reg cell counts were associated to graft survival, while in lung Tx, there is limited evidence for similar findings. This study aims to analyze long term peripheral kinetics of T-reg-cells in a cohort of lung recipients and tests its association to several clinical variables. METHODS: From jan 2009 to dec 2014, 137 lung Tx recipients were submitted to an immunological follow up (median: 105...
July 18, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28719149/cadmium-induced-toxicity-is-rescued-by-curcumin-a-review
#7
REVIEW
Mohammad Mohajeri, Mehdi Rezaee, Amirhossein Sahebkar
Cadmium (Cd) is one of the most common environmental and occupational heavy metals with extended distribution. Exposure to Cd may be associated with several deleterious consequences on the liver, bones, kidneys, lungs, testes, brain, immunological, and cardiovascular systems. Overproduction of reactive oxygen species (ROS) as the main mechanism behind its toxicity causes oxidative stress and subsequent damages to lipids, proteins, and DNA. Therefore, antioxidants along with chelating agents have shown promising outcomes against Cd-induced toxicity...
July 18, 2017: BioFactors
https://www.readbyqxmd.com/read/28719147/human-immunology-studies-using-organ-donors-impact-of-clinical-variations-on-immune-parameters-in-tissues-and-circulation
#8
D J Carpenter, T Granot, N Matsuoka, T Senda, B V Kumar, J J C Thome, C L Gordon, M Miron, J Weiner, T Connors, H Lerner, A Friedman, T Kato, A D Griesemer, D L Farber
Organ donors are sources of physiologically healthy organs and tissues for life-saving transplantation, and have been recently used for human immunology studies which are typically confined to the sampling of peripheral blood. Donors comprise a diverse population with different causes of death and clinical outcomes during hospitalization, and the effects of such variations on immune parameters in blood and tissues are not known. We present here coordinate analyses of innate and adaptive immune components in blood, lymphoid (bone marrow, spleen, lymph nodes), and mucosal (lungs, intestines) sites from a population of brain-dead organ donors (3-months-93-years; n=291) across eight clinical parameters...
July 18, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28716119/stat1-dependent-and-independent-pulmonary-allergic-and-fibrogenic-responses-in-mice-after-exposure-to-tangled-versus-rod-like-multi-walled-carbon-nanotubes
#9
Katherine S Duke, Alexia J Taylor-Just, Mark D Ihrie, Kelly A Shipkowski, Elizabeth A Thompson, Erinn C Dandley, Gregory N Parsons, James C Bonner
BACKGROUND: Pulmonary toxicity of multi-walled carbon nanotubes (MWCNTs) is influenced by physicochemical characteristics and genetic susceptibility. We hypothesized that contrasting rigidities of tangled (t) versus rod-like (r) MWCNTs would result in differing immunologic or fibrogenic responses in mice and that these responses would be exaggerated in transgenic mice lacking the signal transducer and activator of transcription-1 (STAT1), a susceptible mouse model of pulmonary fibrosis...
July 17, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28714780/atezolizumab-for-the-treatment-of-non-small-cell-lung-cancer
#10
Fernando C Santini, Charles M Rudin
The immune system can restrain or promote cancer development and growth. Antibodies targeting immune checkpoints have revolutionized cancer treatment. Among the best responses have been in non-small cell lung cancer (NSCLC) which is largely caused by chronic exposure to carcinogens; associated with high neoantigen creation and sensitization to immune recognition. Atezolizumab was the first approved antibody that targets the PD-1 ligand (PD-L1). Areas Covered: This drug profile article covers the basics of the cancer-immunity cycle and reviews some aspects of innate and adaptive immunology...
July 17, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28714174/immunological-properties-and-protective-efficacy-of-a-single-mycobacterial-antigen-displayed-on-polyhydroxybutyrate-beads
#11
Patricia Rubio-Reyes, Natalie A Parlane, Bryce M Buddle, D Neil Wedlock, Bernd H A Rehm
In 2015, there were an estimated 10.4 million new tuberculosis (TB) cases and 1.4 million deaths worldwide. Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the vaccine available against TB, but it is insufficient for global TB control. This study evaluated the immunogenicity of the Mycobacterium tuberculosis antigen Rv1626 in mice while assessing the effect of co-delivering either Cpe30 (immunostimulatory peptide), CS.T3378-395 (promiscuous T helper epitope) or flagellin (TLR5 agonist) or a combination of all three immunostimulatory agents...
July 17, 2017: Microbial Biotechnology
https://www.readbyqxmd.com/read/28711989/striking-the-right-immunological-balance-prevents-progression-of-tuberculosis
#12
REVIEW
Shachi Pranjal Vyas, Ritobrata Goswami
INTRODUCTION: Tuberculosis (TB) caused by infection with Mycobacterium tuberculosis (Mtb) is a major burden for human health worldwide. Current standard treatments for TB require prolonged administration of antimycobacterial drugs leading to exaggerated inflammation and tissue damage. This can result in the reactivation of latent TB culminating in TB progression. Thus, there is an unmet need to develop therapies that would shorten the duration of anti-TB treatment and to induce optimal protective immune responses to control the spread of mycobacterial infection with minimal lung pathology...
July 15, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28710016/comparative-study-of-immunopathophysiological-responses-induced-by-b-%C3%A2-melitensis-and-its-lipopolysaccharide-in-mouse-model-infected-via-intranasal-route-of-exposure
#13
Abdinasir Yusuf Osman, Abdul Aziz Saharee, Faez Firdaus Jesse, Arifah Abdul Kadir
In this study, we developed a mouse model and characterized the effects of intranasal inoculation of virulent Brucella melitensis strain 16M and its lipopolysaccharide (LPS). The effects of the exposure were compared with respective control groups. Both Brucella melitensis-infected and LPS-infected groups showed no significant clinical presentation with minor relevance in the mortality associated with the infection. In Brucella melitensis-infected group, significant histopathological changes in comparison to the LPS infected group with increase bacterial burden in the lungs, reproductive and reticuloendothelial organs were observed...
July 11, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28709893/regulatory-effect-of-baicalin-on-the-imbalance-of-th17-treg-responses-in-mice-with-allergic-asthma
#14
Lu Xu, Jinxia Li, Yu Zhang, Peng Zhao, Xuemei Zhang
ETHNOPHARMACOLOGY RELEVANCE: Baicalin, a flavonoid compound, was isolated from traditional Chinese medicine Scutellaria baicalensis Georgi. The study aimed to explore the regulatory effect of baicalin on immunological balance of Th17/Treg responses and the possible mechanisms in mice with allergic asthma. MATERIALS AND METHODS: Mice were sensitized and challenged with OVA+LPS by intranasal instillation, and were intragastrically treated with baicalin from days 22-36 after sensitization...
July 12, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28707587/immunotherapeutic-interleukin-6-or-interleukin-6-receptor-blockade-in-cancer-challenges-and-opportunities
#15
Nirmala C Kampan, Sue D Xiang, Orla M McNally, Andrew N Stephens, Michael A Quinn, Magdalena Plebanski
Interleukin 6 (IL-6), a well-known pro-inflammatory cytokine with pleiotropic activity is a central player in chronic inflammatory diseases including cancers. Therefore, blockade of the IL-6 signaling pathway has become a target for the therapy of in diverse cancers such as multicentric Castleman's disease (CD), multiple myeloma and solid tumours including renal, prostate, lung, colorectal and ovarian cancers. Monoclonal antibodies against IL-6 (Siltuximab) and the IL-6 receptor (IL-6R) (Tocilizumab) have emerged as potential immunotherapies, alone or in combination with conventional chemotherapy...
July 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28704651/synergy-between-the-host-immune-system-and-bacteriophage-is-essential-for-successful-phage-therapy-against-an-acute-respiratory-pathogen
#16
Dwayne R Roach, Chung Yin Leung, Marine Henry, Eric Morello, Devika Singh, James P Di Santo, Joshua S Weitz, Laurent Debarbieux
The rise of multi-drug-resistant (MDR) bacteria has spurred renewed interest in the use of bacteriophages in therapy. However, mechanisms contributing to phage-mediated bacterial clearance in an animal host remain unclear. We investigated the effects of host immunity on the efficacy of phage therapy for acute pneumonia caused by MDR Pseudomonas aeruginosa in a mouse model. Comparing efficacies of phage-curative and prophylactic treatments in healthy immunocompetent, MyD88-deficient, lymphocyte-deficient, and neutrophil-depleted murine hosts revealed that neutrophil-phage synergy is essential for the resolution of pneumonia...
July 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28704185/phenotypes-determined-by-cluster-analysis-in-moderate-to-severe-bronchial-asthma
#17
Vania M Youroukova, Denitsa G Dimitrova, Anna D Valerieva, Spaska S Lesichkova, Tsvetelina V Velikova, Ekaterina I Ivanova-Todorova, Kalina D Tumangelova-Yuzeir
BACKGROUND: Bronchial asthma is a heterogeneous disease that includes various subtypes. They may share similar clinical characteristics, but probably have different pathological mechanisms. AIM: To identify phenotypes using cluster analysis in moderate to severe bronchial asthma and to compare differences in clinical, physiological, immunological and inflammatory data between the clusters. PATIENTS AND METHODS: Forty adult patients with moderate to severe bronchial asthma out of exacerbation were included...
June 1, 2017: Folia Medica
https://www.readbyqxmd.com/read/28702025/cellular-and-molecular-defects-underlying-invasive-fungal-infections-revelations-from-endemic-mycoses
#18
REVIEW
Pamela P Lee, Yu-Lung Lau
The global burden of fungal diseases has been increasing, as a result of the expanding number of susceptible individuals including people living with human immunodeficiency virus (HIV), hematopoietic stem cell or organ transplant recipients, patients with malignancies or immunological conditions receiving immunosuppressive treatment, premature neonates, and the elderly. Opportunistic fungal pathogens such as Aspergillus, Candida, Cryptococcus, Rhizopus, and Pneumocystis jiroveci are distributed worldwide and constitute the majority of invasive fungal infections (IFIs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28695368/an-interaction-of-lps-and-rsv-infection-in-augmenting-the-ahr-and-airway-inflammation-in-mice
#19
Na Zhou, Wei Li, Luo Ren, Xiaohong Xie, Enmei Liu
Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infection (LRTI) in children under 5 years of age, especially infants with severe bronchiolitis. Our preliminary clinical experiments showed that bacterial colonization was commonly observed in children with virus-induced wheezing, particularly in those with recurrent wheezing, suggesting that bacterial colonization with an accompanying viral infection may contribute to disease severity. In most cases, RSV-infected infants were colonized with pathogenic bacteria (mainly Gram-negative bacteria)...
July 10, 2017: Inflammation
https://www.readbyqxmd.com/read/28694492/chronic-lung-inflammation-primes-humoral-immunity-and-augments-antipneumococcal-resistance
#20
Julia D Boehme, Sabine Stegemann-Koniszewski, Andrea Autengruber, Nicole Peters, Josef Wissing, Lothar Jänsch, Andreas Jeron, Dunja Bruder
Airway epithelial cells (AECs) display remarkable plasticity in response to infectious stimuli and their functional adaptations are critical for antimicrobial immunity. However, the roles of AECs and humoral mediators to host defense in non-communicable lung inflammation remain elusive. We dissected pulmonary defense against Streptococcus pneumoniae in hosts with pre-existing inflammatory conditions (SPC-HAxTCR-HA mice). Lung tissue transcriptomics and bronchoalveolar lavage fluid (BALF) proteomics revealed an induction of humoral defense mechanisms in inflamed lungs...
July 10, 2017: Scientific Reports
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