title: Peripheral compartment innate immune response to Haemophilus influenzae and Streptococcus pneumoniae in chronic obstructive pulmonary disease patients.
abstract: 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.
authors.affiliation: Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, QLD, Australia. ss.francis@uqconnect.edu.au
authors.forename: Santiyagu M Savarimuthu
authors.initials: SM
authors.lastname: Francis
authors.forename: Maxine E
authors.initials: ME
authors.lastname: Tan
authors.forename: Pamela R
authors.initials: PR
authors.lastname: Fung
authors.forename: Janet G
authors.initials: JG
authors.lastname: Shaw
authors.forename: Annalese Bt
authors.initials: AB
authors.lastname: Semmler
authors.forename: Maria
authors.initials: M
authors.lastname: Nataatmadja
authors.forename: Rayleen V
authors.initials: RV
authors.lastname: Bowman
authors.forename: Kwun M
authors.initials: KM
authors.lastname: Fong
authors.forename: Ian A
authors.initials: IA
authors.lastname: Yang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D006192:Haemophilus Infections / Q000276:immunology*; D006193:Haemophilus influenzae / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000821:virology; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology*; D013290:Streptococcal Infections / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*