title: The host immune response contributes to Haemophilus influenzae virulence.
abstract: BACKGROUND
  There is compelling evidence that infections with non-typeable Haemophilus influenzae (NTHi) are associated with exacerbations in COPD patients. However, NTHi has also been isolated frequently during clinically stable disease. In this study we tested the hypothesis that genetically distinct NTHi isolates obtained from COPD patients differ in virulence which could account for dissimilarities in the final outcome of an infection (stable vs. exacerbation).
  
  
  RESULTS
  NTHi isolates (n = 32) were obtained from stable COPD patients, or during exacerbations. Genetically divergent NTHi isolates were selected and induction of inflammation was assessed as an indicator of virulence using different in vitro models. Despite marked genomic differences among NTHi isolates, in vitro studies could not distinguish between NTHi isolates based on their inflammatory capacities. Alternatively, when using a whole blood assay results demonstrated marked inter-, but not intra-individual differences in cytokine release between healthy volunteers irrespective of the origin of the NTHi isolate used.
  
  
  CONCLUSIONS
  Results suggest that the individual immune reactivity might be an important predictor for the clinical outcome (exacerbation vs. no exacerbation) following NTHi infection.
authors.affiliation: Department of Medical Microbiology, NUTRIM, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, The Netherlands. Electronic address: T.Geelen@maastrichtuniversity.nl.
authors.forename: Tanja H
authors.initials: TH
authors.lastname: Geelen
authors.affiliation: Department of Medical Microbiology, NUTRIM, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, The Netherlands. Electronic address: Giel.Gaajetaan@maastrichtuniversity.nl.
authors.forename: Giel R
authors.initials: GR
authors.lastname: Gaajetaan
authors.affiliation: Department of Respiratory Medicine, NUTRIM, Maastricht University Medical Centre, Maastricht, The Netherlands; Program Development Centre, CIRO+, Horn, The Netherlands. Electronic address: e.wouters@mumc.nl.
authors.forename: Emiel F
authors.initials: EF
authors.lastname: Wouters
authors.affiliation: Department of Respiratory Medicine, NUTRIM, Maastricht University Medical Centre, Maastricht, The Netherlands. Electronic address: g.rohde@mumc.nl.
authors.forename: Gernot G
authors.initials: GG
authors.lastname: Rohde
authors.affiliation: Program Development Centre, CIRO+, Horn, The Netherlands. Electronic address: fritsfranssen@ciro-horn.nl.
authors.forename: Frits M
authors.initials: FM
authors.lastname: Franssen
authors.affiliation: Department of Medical Microbiology, NUTRIM, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, The Netherlands. Electronic address: g.grauls@maastrichtuniversity.nl.
authors.forename: Gert E
authors.initials: GE
authors.lastname: Grauls
authors.affiliation: Department of Medical Microbiology, NUTRIM, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, The Netherlands. Electronic address: e.stobberingh@gmail.com.
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Stobberingh
authors.affiliation: Department of Medical Microbiology, NUTRIM, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, The Netherlands. Electronic address: bruggeman@stintelaar.be.
authors.forename: Cathrien A
authors.initials: CA
authors.lastname: Bruggeman
authors.affiliation: Department of Medical Microbiology, NUTRIM, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, The Netherlands. Electronic address: f.stassen@maastrichtuniversity.nl.
authors.forename: Frank R
authors.initials: FR
authors.lastname: Stassen
mesh_terms: D000368:Aged; D015992:Body Mass Index; D018450:Disease Progression; D005260:Female; D006192:Haemophilus Infections / Q000150:complications / Q000175:diagnosis / Q000276:immunology*; D006193:Haemophilus influenzae / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000276:immunology* / Q000382:microbiology / Q000534:rehabilitation; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
keywords: Chronic obstructive pulmonary disease; Exacerbations; Inflammatory response; Non-typeable Haemophilus influenzae