Peripheral compartment innate immune response to Haemophilus influenzae and Streptococcus pneumoniae in chronic obstructive pulmonary disease patients

Alterations in innate immunity that predispose to chronic obstructive pulmonary disease (COPD) exacerbations are poorly understood. We examined innate immunity gene expression in peripheral blood polymorphonuclear leukocytes (PMN) and monocytes stimulated by Haemophilus influenzae and Streptococcus pneumoniae. Thirty COPD patients (15 rapid and 15 non-rapid lung function decliners) and 15 smokers without COPD were studied. Protein expression of IL-8, IL-6, TNF-α and IFN-γ (especially monocytes) increased with bacterial challenge. In monocytes stimulated with S. pneumoniae, TNF-α protein expression was higher in COPD (non-rapid decliners) than in smokers. In co-cultures of monocytes and PMN, mRNA expression of TGF-β1 and MYD88 was up-regulated, and CD14, TLR2 and IFN-γ down-regulated with H. influenzae challenge. TNF-α mRNA expression was increased with H. influenzae challenge in COPD. Cytokine responses were similar between rapid and non-rapid decliners. TNF-α expression was up-regulated in non-rapid decliners in response to H. influenzae (monocytes) and S. pneumoniae (co-culture of monocytes and PMN). Exposure to bacterial pathogens causes characteristic innate immune responses in peripheral blood monocytes and PMN in COPD. Bacterial exposure significantly alters the expression of TNF-α in COPD patients, although not consistently. There did not appear to be major differences in innate immune responses between rapid and non-rapid decliners.

[1]  L. Palmberg,et al.  Chemokine release by neutrophils in chronic obstructive pulmonary disease , 2012, Innate immunity.

[2]  J. Søndergaard,et al.  Divergent Pro-Inflammatory Profile of Human Dendritic Cells in Response to Commensal and Pathogenic Bacteria Associated with the Airway Microbiota , 2012, PloS one.

[3]  L. Edwards,et al.  Changes in forced expiratory volume in 1 second over time in COPD. , 2011, The New England journal of medicine.

[4]  Christopher E Brightling,et al.  Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers. , 2011, American journal of respiratory and critical care medicine.

[5]  G. Joos,et al.  Chronic Obstructive Pulmonary Disease 1 New insights into the immunology of chronic obstructive pulmonary disease , 2011 .

[6]  J. Bengoechea,et al.  Impact of cigarette smoke exposure on host–bacterial pathogen interactions , 2011, European Respiratory Journal.

[7]  B. Cosío,et al.  Mecanismos moleculares de inflamación durante las agudizaciones de la enfermedad pulmonar obstructiva crónica , 2011 .

[8]  P. Gibson,et al.  Innate Immune Responses Are Increased in Chronic Obstructive Pulmonary Disease , 2011, PloS one.

[9]  Laszlo Nagy,et al.  Chronic Obstructive Pulmonary Disease-Specific Gene Expression Signatures of Alveolar Macrophages as well as Peripheral Blood Monocytes Overlap and Correlate with Lung Function , 2011, Respiration.

[10]  J. Curtis,et al.  Analysis of the Lung Microbiome in the “Healthy” Smoker and in COPD , 2011, PloS one.

[11]  S. Sethi,et al.  Nontypeable Haemophilus influenzae in chronic obstructive pulmonary disease and lung cancer , 2011, International journal of chronic obstructive pulmonary disease.

[12]  A. Agustí,et al.  Molecular mechanisms of inflammation during exacerbations of chronic obstructive pulmonary disease. , 2011, Archivos de bronconeumologia.

[13]  J. Wedzicha,et al.  Susceptibility to exacerbation in chronic obstructive pulmonary disease. , 2010, The New England journal of medicine.

[14]  L. Palmberg,et al.  Altered innate immune response in farmers and smokers , 2010, Innate immunity.

[15]  S. Salvi,et al.  Year‐in‐review 2009: Asthma, COPD and airway biology , 2010, Respirology.

[16]  J. Wedzicha,et al.  Defective macrophage phagocytosis of bacteria in COPD , 2009, European Respiratory Journal.

[17]  M. Decramer,et al.  Effect of tiotropium on outcomes in patients with moderate chronic obstructive pulmonary disease (UPLIFT): a prespecified subgroup analysis of a randomised controlled trial , 2009, The Lancet.

[18]  Min Han,et al.  Impact of Cigarette Smoke Exposure on Innate Immunity: A Caenorhabditis elegans Model , 2009, PloS one.

[19]  J. Houwing-Duistermaat,et al.  IL6 and CRP haplotypes are associated with COPD risk and systemic inflammation: a case-control study , 2009, BMC Medical Genetics.

[20]  S. Diamond,et al.  Neutrophil Isolation Protocol , 2008, Journal of visualized experiments : JoVE.

[21]  D. Postma,et al.  Airways inflammation and treatment during acute exacerbations of COPD , 2008, International journal of chronic obstructive pulmonary disease.

[22]  F. Mihălțan,et al.  Anti-TNF-alpha therapies in chronic obstructive pulmonary diseases. , 2008, Expert opinion on investigational drugs.

[23]  B. Celli,et al.  Impact of COPD exacerbations on patient-centered outcomes. , 2007, Chest.

[24]  Bartolome Celli,et al.  Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. , 2007, The New England journal of medicine.

[25]  K. Heeg,et al.  Differences in innate immune responses upon stimulation with gram-positive and gram-negative bacteria. , 2006, Journal of periodontal research.

[26]  S. Paludan,et al.  Live Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis activate the inflammatory response through Toll‐like receptors 2, 4, and 9 in species‐specific patterns , 2006, Journal of leukocyte biology.

[27]  P. Wallace,et al.  Impaired alveolar macrophage response to Haemophilus antigens in chronic obstructive lung disease. , 2006, American journal of respiratory and critical care medicine.

[28]  L. Fabbri,et al.  Pathophysiology of exacerbations of chronic obstructive pulmonary disease. , 2006, Proceedings of the American Thoracic Society.

[29]  A. Agustí,et al.  Expression of Toll-like receptor 2 is up-regulated in monocytes from patients with chronic obstructive pulmonary disease , 2006, Respiratory research.

[30]  G. Donaldson,et al.  MMP-9, TIMP-1 and inflammatory cells in sputum from COPD patients during exacerbation , 2005, Respiratory research.

[31]  T. Seemungal,et al.  Airway and Systemic Inflammation and Decline in Lung Function in Patients With COPD , 2005, Chest.

[32]  J. Hankinson,et al.  Standardisation of spirometry , 2005, European Respiratory Journal.

[33]  A. Unlu,et al.  Leptin and TNF-Alpha Levels in Patients with Chronic Obstructive Pulmonary Disease and Their Relationship to Nutritional Parameters , 2004, Respiration.

[34]  H. Baker,et al.  Molecular Characterization of the Acute Inflammatory Response to Infections with Gram-Negative versus Gram-Positive Bacteria , 2003, Infection and Immunity.

[35]  E. Piitulainen,et al.  Circulating monocytes from healthy individuals and COPD patients , 2003, Respiratory research.

[36]  A. Lacy-Hulbert,et al.  Apoptotic Cells and Innate Immune Stimuli Combine to Regulate Macrophage Cytokine Secretion 1 , 2003, The Journal of Immunology.

[37]  P. Zimmerman,et al.  Mannose-binding lectin gene polymorphism predicts hospital admissions for COPD infections , 2003, Genes and Immunity.

[38]  L. Fabbri,et al.  Nuclear localisation of p65 in sputum macrophages but not in sputum neutrophils during COPD exacerbations. , 2003, Thorax.

[39]  E. Rönmark,et al.  The costs of exacerbations in chronic obstructive pulmonary disease (COPD). , 2002, Respiratory medicine.

[40]  Ash A. Alizadeh,et al.  Stereotyped and specific gene expression programs in human innate immune responses to bacteria , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[41]  M. Pfaffl,et al.  A new mathematical model for relative quantification in real-time RT-PCR. , 2001, Nucleic acids research.

[42]  K. Wright,et al.  Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease. , 2001, American journal of respiratory and critical care medicine.

[43]  R. Stockley,et al.  Association between airway bacterial load and markers of airway inflammation in patients with stable chronic bronchitis. , 2000, The American journal of medicine.

[44]  R. van Furth,et al.  Anti-CD14 Monoclonal Antibodies Inhibit the Production of Tumor Necrosis Factor Alpha and Interleukin-10 by Human Monocytes Stimulated with Killed and Live Haemophilus influenzae or Streptococcus pneumoniaeOrganisms , 1999, Infection and Immunity.

[45]  R. Rogers,et al.  Elevated TNF-alpha production by peripheral blood monocytes of weight-losing COPD patients. , 1996, American journal of respiratory and critical care medicine.

[46]  C. McCall,et al.  Phagocytosis of Live Versus Heat-Killed Bacteria by Human Polymorphonuclear Leukocytes , 1974, Infection and immunity.