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Journal articleMakris S, Paulsen M, Johansson C, 2017,
Type I interferons as regulators of lung inflammation
, Frontiers in Immunology, Vol: 8, ISSN: 1664-3224Immune responses to lung infections must be tightly regulated in order to permit pathogen eradication while maintaining organ function. Exuberant or dysregulated inflammation can impair gas exchange and underlies many instances of lung disease. An important driver of inflammation in the lung is the interferon (IFN) response. Type I IFNs are anti-viral cytokines that induce a large range of proteins that impair viral replication in infected cells. This cell-intrinsic action plays a crucial role in protecting the lungs from spread of respiratory viruses. However, type I IFNs have also recently been found to be central to the initiation of lung inflammatory responses, by inducing recruitment and activation of immune cells. This helps control virus burden but can cause detrimental immunopathology and contribute to disease severity. Furthermore, there is now increasing evidence that type I IFNs are not only induced after viral infections but also after infection with bacteria and fungi. The pro-inflammatory function of type I IFNs in the lung opens up the possibility of immune modulation directed against this anti-viral cytokine family. In this review, the initiation and signaling of type I IFNs as well as their role in driving and maintaining lung inflammation will be discussed.
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Journal articleOpenshaw PJM, 2017,
RSV takes control of neonatal Breg cells: two hands on the wheel
, Immunity, Vol: 46, Pages: 171-173, ISSN: 1074-7613The viral attachment protein of RSV has many surprising features, especially its mimicry of fractalkine (CX3CL1). Zhivaki et al. (2017) now show that, in addition to using this homology to attach to ciliated cells, it activates human neonatal regulatory B cells, thereby inhibiting immunological responses.
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Journal articleOpenshaw PJM, Chiu C, Culley FJ, et al., 2017,
Protective and Harmful Immunity to RSV Infection
, Annual Review of Immunology, Vol: 35, Pages: 501-532, ISSN: 0732-0582Respiratory syncytial virus (RSV) is an exceptional mucosal pathogen. It specializes in infection of the ciliated respiratory epithelium, causing disease of variable severity with little or no direct systemic effects. It infects virtually all children by the age of three years and then repeatedly infects throughout life; this it does despite relatively slight variations in antigenicity, apparently by inducing selective immunological amnesia. Inappropriate or dysregulated responses to RSV can be pathogenic, causing disease-enhancing inflammation that contributes to short- and long-term effects. In addition, RSV's importance as a largely unrecognized pathogen of debilitated older people is increasingly evident. Vaccines that induce nonpathogenic protective immunity may soon be available, and it is possible that different vaccines will be optimal for infants; older children; young to middle-age adults (including pregnant women); and elderly persons. At the dawn of RSV vaccination, it is timely to review what is known (and unknown) about immune responses to this fascinating virus.
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Conference paperThwaites RS, Gunawardana NC, Broich VL, et al., 2017,
Activation of the complement, coagulation and fibrinolysis pathways after nasal allergen challenge
, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: Elsevier, Pages: AB384-AB384, ISSN: 0091-6749 -
Conference paperGunawardana NC, Jain A, Zhao Q, et al., 2017,
Biomarkers of 12 SQ House Dust Mite Sublingual Immunotherapy (SLIT)-Tablet Treatment After Nasal Allergen Challenge
, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB192-AB192, ISSN: 0091-6749 -
Journal articleFarrell PM, White TB, Howenstine MS, et al., 2017,
Diagnosis of Cystic Fibrosis in Screened Populations
, JOURNAL OF PEDIATRICS, Vol: 181, Pages: S33-+, ISSN: 0022-3476 -
Journal articleNg-Blichfeldt JP, Alçada J, Montero MA, et al., 2017,
Deficient retinoid-driven angiogenesis may contribute to failure of adult human lung regeneration in emphysema
, Thorax, Vol: 72, Pages: 510-521, ISSN: 0040-6376BACKGROUND: Molecular pathways that regulate alveolar development and adult repair represent potential therapeutic targets for emphysema. Signalling via retinoic acid (RA), derived from vitamin A, is required for mammalian alveologenesis, and exogenous RA can induce alveolar regeneration in rodents. Little is known about RA signalling in the human lung and its potential role in lung disease. OBJECTIVES: To examine regulation of human alveolar epithelial and endothelial repair by RA, and characterise RA signalling in human emphysema. METHODS: The role of RA signalling in alveolar epithelial repair was investigated with a scratch assay using an alveolar cell line (A549) and primary human alveolar type 2 (AT2) cells from resected lung, and the role in angiogenesis using a tube formation assay with human lung microvascular endothelial cells (HLMVEC). Localisation of RA synthetic (RALDH-1) and degrading (cytochrome P450 subfamily 26 A1 (CYP26A1)) enzymes in human lung was determined by immunofluorescence. Regulation of RA pathway components was investigated in emphysematous and control human lung tissue by quantitative real-time PCR and Western analysis. RESULTS: RA stimulated HLMVEC angiogenesis in vitro; this was partially reproduced with a RAR-α agonist. RA induced mRNA expression of vascular endothelial growth factor A (VEGFA) and VEGFR2. RA did not modulate AT2 repair. CYP26A1 protein was identified in human lung microvasculature, whereas RALDH-1 partially co-localised with vimentin-positive fibroblasts. CYP26A1 mRNA and protein were increased in emphysema. CONCLUSIONS: RA regulates lung microvascular angiogenesis; the endothelium produces CYP26A1 which is increased in emphysema, possibly leading to reduced RA availability. These data highlight a role for RA in maintenance of the human pulmonary microvascular endothelium.
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Journal articleDhariwal J, Cameron A, Trujillo-Torralbo MB, et al., 2017,
Mucosal type 2 innate lymphoid cells are a key component of the allergic response to aeroallergen
, American Journal of Respiratory and Critical Care Medicine, Vol: 195, Pages: 1586-1596, ISSN: 1535-4970RATIONALE: Newly characterised type 2 innate lymphoid cells display potent type 2 effector functionality, however their contribution to allergic airways inflammation and asthma is poorly understood. Mucosal biopsy used to characterise the airway mucosa is invasive, poorly tolerated and does not allow sequential sampling. OBJECTIVES: To assess the role of type 2 innate lymphoid cells during nasal allergen challenge in subjects with allergic rhinitis, using novel non-invasive methodology. METHODS: We used a human experimental allergen challenge model, with flow cytometric analysis of nasal curettage samples, to assess the recruitment of type 2 innate lymphoid cells and granulocytes to the upper airways of atopic and healthy subjects following allergen provocation. Soluble mediators in the nasal lining fluid were measured using nasosorption. MEASUREMENTS AND MAIN RESULTS: Following allergen challenge, atopic subjects displayed rapid induction of upper airway symptoms, an enrichment of type 2 innate lymphoid cells, eosinophils and neutrophils, along with increased production of interleukin-5, prostaglandin D2, and eosinophil and T-helper type 2 cell chemokines compared to healthy subjects. The most pronounced type 2 innate lymphoid cell recruitment was observed in patients with elevated serum IgE and airway eosinophilia. CONCLUSIONS: The rapid recruitment of type 2 innate lymphoid cells to the upper airways of allergic rhinitis patients, and their association with key type 2 mediators, highlights their likely important role in the early allergic response to aeroallergen in the airways. The novel methodology described herein enables the analysis of rare cell populations from non-invasive, serial tissue sampling.
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Journal articleBernal P, Allsopp LP, Filloux AAM, et al., 2017,
The Pseudomonas putida T6SS is a plant warden against phytopathogens
, The ISME Journal, Vol: 11, Pages: 972-987, ISSN: 1751-7362Bacterial type VI secretion systems (T6SSs) are molecular weapons designed to deliver toxic effectors into prey cells. These nanomachines play an important role in inter-bacterial competition and provide advantages to T6SS active strains in polymicrobial environments. Here we analyse the genome of the biocontrol agent Pseudomonas putida KT2440 and identify three T6SS gene clusters (K1-, K2- and K3-T6SS). Besides, ten T6SS effector/immunity pairs were found, including putative nucleases and pore-forming colicins. We show that the K1-T6SS is a potent antibacterial device which secretes a toxic Rhs-type effector Tke2. Remarkably, P. putida eradicates a broad range of bacteria in a K1-T6SS-dependent manner, including resilient phytopathogens which demonstrates that the T6SS is instrumental to empower P. putida to fight against competitors. Furthermore, we observed a drastically reduced necrosis on the leaves of Nicotiana benthamiana during co-infection with P. putida and Xanthomonas campestris. Such protection is dependent on the activity of the P. putida T6SS. Many routes have been explored to develop biocontrol agents capable of manipulating the microbial composition of the rhizosphere and phyllosphere. Here we unveil a novel mechanism for plant biocontrol which needs to be considered for the selection of plant wardens whose mission is to prevent phytopathogen infections.
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Journal articleJohansson C, 2016,
Respiratory syncytial virus infection: an innate perspective.
, F1000Research, Vol: 5, ISSN: 2046-1402Respiratory syncytial virus (RSV) is a common cause of upper respiratory tract infection in children and adults. However, infection with this virus sometimes leads to severe lower respiratory disease and is the major cause of infant hospitalisations in the developed world. Several risk factors such as baby prematurity and congenital heart disease are known to predispose towards severe disease but previously healthy, full-term infants can also develop bronchiolitis and viral pneumonia during RSV infection. The causes of severe disease are not fully understood but may include dysregulation of the immune response to the virus, resulting in excessive recruitment and activation of innate and adaptive immune cells that can cause damage. This review highlights recent discoveries on the balancing act of immune-mediated virus clearance versus immunopathology during RSV infection.
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