Publications
753 results found
Bright PD, Smith L, Usher J, et al., 2015, False interpretation of diagnostic serology tests for patients treated with pooled human immunoglobulin G infusions: a trap for the unwary, CLINICAL MEDICINE, Vol: 15, Pages: 125-129, ISSN: 1470-2118
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- Citations: 24
Glanville N, Johnston SL, 2015, Challenges in developing a cross-serotype rhinovirus vaccine, Current Opinion in Virology, Vol: 11, Pages: 83-88, ISSN: 1879-6257
A great burden of disease is attributable to human rhinovirus (HRV) infections which are the major cause of the common cold, exacerbations of both asthma and chronic obstructive pulmonary disease (COPD), and are associated with asthma development. Despite this there is currently no vaccine for HRV. The first vaccine studies showed some promise in terms of serotype-specific protection against cold symptoms, but antigenic heterogeneity amongst the >150 HRVs has been regarded as a major barrier to effective vaccine development and has resulted in little progress over 50 years. Here we review those vaccine studies conducted to date, discuss the difficulties posed by antigenic heterogeneity and describe some recent advances in generating cross-reactive antibodies and T cell responses using peptide immunogens.
Schapowal A, Klein P, Johnston SL, 2015, Echinacea Reduces the Risk of Recurrent Respiratory Tract Infections and Complications: A Meta-Analysis of Randomized Controlled Trials, ADVANCES IN THERAPY, Vol: 32, Pages: 187-200, ISSN: 0741-238X
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- Citations: 35
Singanayagam A, Glanville N, Bartlett N, et al., 2015, Effect of fluticasone propionate on virus-induced airways inflammation and anti-viral immune responses in mice, Spring Meeting on Clinician Scientists in Training, Publisher: ELSEVIER SCIENCE INC, Pages: 88-88, ISSN: 0140-6736
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- Citations: 4
Drysdale SB, Alcazar-Paris M, Wilson T, et al., 2015, Viral lower respiratory tract infections and preterm infants' healthcare utilisation, EUROPEAN JOURNAL OF PEDIATRICS, Vol: 174, Pages: 209-215, ISSN: 0340-6199
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- Citations: 18
Schogler A, Kopf BS, Edwards MR, et al., 2015, Novel antiviral properties of azithromycin in cystic fibrosis airway epithelial cells, EUROPEAN RESPIRATORY JOURNAL, Vol: 45, Pages: 428-439, ISSN: 0903-1936
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- Citations: 105
Cameron A, Dhariwal J, Johnston SL, et al., 2015, Rhinovirus Modulation of Dendritic Cell Phenotype and Function, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB63-AB63, ISSN: 0091-6749
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- Citations: 1
Lan F, Zhang N, Holtappels G, et al., 2015, Staphyloccoccus Aureus Induces a Th2 Response Via TSLP and IL-33 Release in Human Airway Mucosa, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB81-AB81, ISSN: 0091-6749
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- Citations: 1
Singanayagam A, Johnston SL, Mallia P, 2015, Inhaled Glucocorticoids and COPD Exacerbations, New England Journal of Medicine, Vol: 372, Pages: 92-93, ISSN: 1533-4406
Bright PD, Rooney N, Virgo PF, et al., 2015, Laboratory clues to immunodeficiency; missed chances for early diagnosis?, JOURNAL OF CLINICAL PATHOLOGY, Vol: 68, Pages: 1-5, ISSN: 0021-9746
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- Citations: 14
Finney LJ, Toussaint M, Calderazzo M, et al., 2015, Bacterial Load In Stable And Exacerbated COPD, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Toussaint M, Footitt J, Trujillo-Torralbo M-B, et al., 2015, Airway Dna Levels In Virus-Induced COPD Exacerbations, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Bartlett NW, Singanayagam A, Johnston SL, 2015, Mouse Models of Rhinovirus Infection and Airways Disease, RHINOVIRUSES: METHODS AND PROTOCOLS, Vol: 1221, Pages: 181-188, ISSN: 1064-3745
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- Citations: 15
Hilzendeger C, Da Silva J, Henket M, et al., 2015, Expression Of Interferons And Interferon-Stimulated Genes In Peripheral-Blood Neutrophils From COPD Patients, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Almond MH, Bakhsoliani E, Edwards MR, et al., 2015, Obesity Is Associated With Decreased Expression Of Suppressor Of Cytokine Signalling 3 In Human Alveolar Macrophages, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Calderazzo M, Trujillo-Torralbo M, Finney LJ, et al., 2015, Relationship Between Viral Colds And COPD Exacerbations, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Teo SM, Mok D, Pham K, et al., 2014, The infant airway microbiome in health and disease impacts later asthma development
<jats:p>The nasopharynx (NP) is a reservoir for microbes associated with acute respiratory illnesses (ARI). The development of asthma is initiated during infancy, driven by airway inflammation associated with infections. Here, we report viral and bacterial community profiling of NP aspirates across a birth cohort, capturing all lower respiratory illnesses during their first year. Most infants were initially colonized with Staphylococcus or Corynebacterium before stable colonization with Alloiococcus or Moraxella, with transient incursions of Streptococcus, Moraxella or Haemophilus marking virus-associated ARIs. Our data identify the NP microbiome as a determinant for infection spread to the lower airways, severity of accompanying inflammatory symptoms, and risk for future asthma development. Early asymptomatic colonization with Streptococcus was a strong asthma predictor, and antibiotic usage disrupted asymptomatic colonization patterns.</jats:p>
Jozwik A, Habibi M, Paras A, et al., 2014, Human T-cell responses to RSV infection in the lower airway, IMMUNOLOGY, Vol: 143, Pages: 76-76, ISSN: 0019-2805
Johnston SL, Zdrenghea MT, Makrinioti H, et al., 2014, The role of macrophage IL-10/innate IFN interplay during virus-induced asthma, Reviews in Medical Virology, Vol: 25, Pages: 33-49, ISSN: 1099-1654
Activation through different signaling pathways results in two functionally different types of macrophages, the pro-inflammatory (M1) and the anti-inflammatory (M2). The polarization of macrophages toward the pro-inflammatory M1 phenotype is considered to be critical for efficient antiviral immune responses in the lung.Among the various cell types that are present in the asthmatic airways, macrophages have emerged as significant participants in disease pathogenesis, because of their activation during both the inflammatory and resolution phases, with an impact on disease progression. Polarized M1 and M2 macrophages are able to reversibly undergo functional redifferentiation into anti-inflammatory or pro-inflammatory macrophages, respectively, and therefore, macrophages mediate both processes.Recent studies have indicated a predominance of M2 macrophages in asthmatic airways. During a virus infection, it is likely that M2 macrophages would secrete higher amounts of the suppressor cytokine IL-10, and less innate IFNs. However, the interactions between IL-10 and innate IFNs during virus-induced exacerbations of asthma have not been well studied.The possible role of IL-10 as a therapy in allergic asthma has already been suggested, but the divergent roles of this suppressor molecule in the antiviral immune response raise concerns. This review attempts to shed light on macrophage IL-10–IFNs interactions and discusses the role of IL-10 in virus-induced asthma exacerbations. Whereas IL-10 is important in terminating pro-inflammatory and antiviral immune responses, the presence of this immune regulatory cytokine at the beginning of virus infection could impair the response to viruses and play a role in virus-induced asthma exacerbations.
Niespodziana K, Cabauatan CR, Jackson DJ, et al., 2014, Rhinovirus-induced VP1-specific Antibodies are Group-specific and Associated With Severity of Respiratory Symptoms., EBioMedicine, Vol: 2, Pages: 64-70, ISSN: 2352-3964
BACKGROUND: Rhinoviruses (RVs) are a major cause of common colds and induce exacerbations of asthma and chronic inflammatory lung diseases. METHODS: We expressed and purified recombinant RV coat proteins VP1-4, non-structural proteins as well as N-terminal fragments of VP1 from four RV strains (RV14, 16, 89, C) covering the three known RV groups (RV-A, RV-B and RV-C) and measured specific IgG-subclass-, IgA- and IgM-responses by ELISA in subjects with different severities of asthma or without asthma before and after experimental infection with RV16. FINDINGS: Before infection subjects showed IgG1 > IgA > IgM > IgG3 cross-reactivity with N-terminal fragments from the representative VP1 proteins of the three RV groups. Antibody levels were higher in the asthmatic group as compared to the non-asthmatic subjects. Six weeks after infection with RV16, IgG1 antibodies showed a group-specific increase towards the N-terminal VP1 fragment, but not towards other capsid and non-structural proteins, which was highest in subjects with severe upper and lower respiratory symptoms. INTERPRETATION: Our results demonstrate that increases of antibodies towards the VP1 N-terminus are group-specific and associated with severity of respiratory symptoms and suggest that it may be possible to develop serological tests for identifying causative RV groups.
Drysdale SB, Lo J, Prendergast M, et al., 2014, Lung function of preterm infants before and after viral infections, EUROPEAN JOURNAL OF PEDIATRICS, Vol: 173, Pages: 1497-1504, ISSN: 0340-6199
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- Citations: 26
Finney L, Berry M, Singanayagam A, et al., 2014, Inhaled corticosteroids and pneumonia in chronic obstructive pulmonary disease, LANCET RESPIRATORY MEDICINE, Vol: 2, Pages: 919-932, ISSN: 2213-2600
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- Citations: 55
Jackson DJ, Makrinioti H, Rana BMJ, et al., 2014, IL-33-dependent Type 2 inflammation during rhinovirus-induced asthma exacerbations in vivo, American Journal of Respiratory and Critical Care Medicine, Vol: 190, Pages: 1373-1382, ISSN: 1535-4970
Rationale: Rhinoviruses are the major cause of asthmaexacerbations; however, its underlying mechanisms are poorlyunderstood. We hypothesized that the epithelial cell–derivedcytokine IL-33 plays a central role in exacerbation pathogenesisthrough augmentation of type 2 inflammation.Objectives: To assess whether rhinovirus induces a type 2inflammatory response in asthma in vivo and to define a role for IL-33in this pathway.Methods: We used a human experimental model of rhinovirusinfection and novel airway sampling techniques to measure IL-4, IL-5,IL-13, and IL-33 levels in the asthmatic and healthy airways duringa rhinovirus infection. Additionally, we cultured human T cells and type2 innate lymphoid cells (ILC2s) with the supernatants of rhinovirusinfectedbronchial epithelial cells (BECs) to assess type 2 cytokineproduction in the presence or absence of IL-33 receptor blockade.Measurements and Main Results: IL-4, IL-5, IL-13, and IL-33 areall induced by rhinovirus in the asthmatic airway in vivo and relate toexacerbation severity. Further, induction of IL-33 correlates withviral load and IL-5 and IL-13 levels. Rhinovirus infection of humanprimary BECs induced IL-33, and culture of human T cells and ILC2swith supernatants of rhinovirus-infected BECs strongly inducedtype 2 cytokines. This induction was entirely dependent on IL-33.Conclusions: IL-33 and type 2 cytokines are induced duringa rhinovirus-induced asthma exacerbation in vivo. Virus-inducedIL-33 and IL-33–responsive T cells and ILC2s are key mechanisticlinks between viral infection and exacerbation of asthma. IL-33inhibition is a novel therapeutic approach for asthma exacerbations
Molyneaux PL, Cox MJ, Willis-Owen SAG, et al., 2014, The role of bacteria in the pathogenesis and progression of idiopathic pulmonary fibrosis, American Journal of Respiratory and Critical Care Medicine, Vol: 190, Pages: 906-913, ISSN: 1535-4970
Rationale:Idiopathic pulmonaryfibrosis (IPF)isa progressivelung diseaseof unknown cause that leads to respiratory failure and death within 5 yearsof diagnosis. Overt respiratory infection and immunosuppression carrya high morbidity and mortality, and polymorphisms in genes related toepithelial integrity and host defense predispose to IPF.Objectives: To investigate the role of bacteria in the pathogenesisand progression of IPF.Methods: We prospectively enrolled patients diagnosed with IPFaccording to international criteria together with healthy smokers,nonsmokers, and subjectswithmoderate chronic obstructive pulmonarydisease as control subjects. Subjects underwent bronchoalveolarlavage (BAL), from which genomic DNA was isolated. The V3–V5region of the bacterial 16S rRNA gene was amplified, allowingquantification of bacterial load and identification of communities by 16SrRNA quantitative polymerase chain reaction and pyrosequencing. Measurements and Main Results: Sixty-five patients with IPFhad double the burden of bacteria in BAL fluid compared with 44 controlsubjects. Baseline bacterial burden predicted the rate of decline in lungvolume and risk of death and associated independently with thers35705950 polymorphism of the MUC5B mucin gene, a proven hostsusceptibilityfactorfor IPF. Sequencing yielded912,883 high-quality readsfrom all subjects.WeidentifiedHaemophilus, Streptococcus,Neisseria, andVeillonella spp. to be more abundant in cases than control subjects.Regression analyses indicated that these specific operational taxonomicunits as well as bacterial burden associated independently with IPF.Conclusions: IPF is characterized by an increased bacterial burdenin BAL that predicts decline in lung function and death. Trials ofantimicrobial therapy are needed to determine if microbial burdenis pathogenic in the disease.
Finney LJ, Ritchie A, Pollard E, et al., 2014, Lower airway colonization and inflammatory response in COPD: a focus on Haemophilus influenzae, International Journal of Chronic Obstructive Pulmonary Disease, Vol: 9, Pages: 1119-1132, ISSN: 1176-9106
Bacterial infection of the lower respiratory tract in chronic obstructive pulmonary disease (COPD) patients is common both in stable patients and during acute exacerbations. The most frequent bacteria detected in COPD patients is Haemophilus influenzae, and it appears this organism is uniquely adapted to exploit immune deficiencies associated with COPD and to establish persistent infection in the lower respiratory tract. The presence of bacteria in the lower respiratory tract in stable COPD is termed colonization; however, there is increasing evidence that this is not an innocuous phenomenon but is associated with airway inflammation, increased symptoms, and increased risk for exacerbations. In this review, we discuss host immunity that offers protection against H. influenzae and how disturbance of these mechanisms, combined with pathogen mechanisms of immune evasion, promote persistence of H. influenzae in the lower airways in COPD. In addition, we examine the role of H. influenzae in COPD exacerbations, as well as interactions between H. influenzae and respiratory virus infections, and review the role of treatments and their effect on COPD outcomes. This review focuses predominantly on data derived from human studies but will refer to animal studies where they contribute to understanding the disease in humans.
Beale J, Jayaraman A, Jackson DJ, et al., 2014, Rhinovirus-induced IL-25 in asthma exacerbation drives type 2 immunity and allergic pulmonary inflammation, Science Translational Medicine, Vol: 6, ISSN: 1946-6234
Rhinoviruses (RVs), which are the most common cause of virally induced asthma exacerbations, account for much of the burden of asthma in terms of morbidity, mortality, and associated cost. Interleukin-25 (IL-25) activates type 2–driven inflammation and is therefore potentially important in virally induced asthma exacerbations. To investigate this, we examined whether RV-induced IL-25 could contribute to asthma exacerbations. RV-infected cultured asthmatic bronchial epithelial cells exhibited a heightened intrinsic capacity for IL-25 expression, which correlated with donor atopic status. In vivo human IL-25 expression was greater in asthmatics at baseline and during experimental RV infection. In addition, in mice, RV infection induced IL-25 expression and augmented allergen-induced IL-25. Blockade of the IL-25 receptor reduced many RV-induced exacerbation-specific responses including type 2 cytokine expression, mucus production, and recruitment of eosinophils, neutrophils, basophils, and T and non-T type 2 cells. Therefore, asthmatic epithelial cells have an increased intrinsic capacity for expression of a pro–type 2 cytokine in response to a viral infection, and IL-25 is a key mediator of RV-induced exacerbations of pulmonary inflammation.
Tsoumakidou M, Tousa S, Semitekolou M, et al., 2014, Tolerogenic signaling by pulmonary CD1c<SUP>+</SUP> dendritic cells induces regulatory T cells in patients with chronic obstructive pulmonary disease by IL-27/IL-10/inducible costimulator ligand, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 134, Pages: 944-U282, ISSN: 0091-6749
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- Citations: 32
Mousnier A, Swieboda D, Pinto A, et al., 2014, Human Rhinovirus 16 Causes Golgi Apparatus Fragmentation without Blocking Protein Secretion, JOURNAL OF VIROLOGY, Vol: 88, Pages: 11671-11685, ISSN: 0022-538X
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- Citations: 22
Jayaraman A, Jackson DJ, Message SD, et al., 2014, IL-15 complexes induce NK- and T-cell responses independent of type I IFN signaling during rhinovirus infection, MUCOSAL IMMUNOLOGY, Vol: 7, Pages: 1151-1164, ISSN: 1933-0219
Rhinoviruses are among the most common viruses to infect man, causing a range of serious respiratory diseases including exacerbations of asthma and COPD. Type I IFN and IL-15 are thought to be required for antiviral immunity; however, their function during rhinovirus infection in vivo is undefined. In RV-infected human volunteers, IL-15 protein expression in fluid from the nasal mucosa and in bronchial biopsies was increased. In mice, RV induced type I IFN-dependent expressions of IL-15 and IL-15Rα, which in turn were required for NK- and CD8+ T-cell responses. Treatment with IL-15–IL-15Rα complexes (IL-15c) boosted RV-induced expression of IL-15, IL-15Rα, IFN-γ, CXCL9, and CXCL10 followed by recruitment of activated, IFN-γ-expressing NK, CD8+, and CD4+ T cells. Treating infected IFNAR1−/− mice with IL-15c similarly increased IL-15, IL-15Rα, IFN-γ, and CXCL9 (but not CXCL10) expression also followed by NK-, CD8+-, and CD4+-T-cell recruitment and activation. We have demonstrated that type I IFN-induced IFN-γ and cellular immunity to RV was mediated by IL-15 and IL-15Rα. Importantly, we also show that IL-15 could be induced via a type I IFN-independent mechanism by IL-15 complex treatment, which in turn was sufficient to drive IFN-γ expression and lymphocyte responses.
Wolsk HM, Folsgaard N, Birch S, et al., 2014, The presence of viruses alters the immune signature in the airway of asymptomatic neonates, European-Academy-of-Allergy-and-Clinical-Immunology Congress, Publisher: WILEY-BLACKWELL, Pages: 192-193, ISSN: 0105-4538
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