title: Haemophilus influenzae increases the susceptibility and inflammatory response of airway epithelial cells to viral infections.
abstract: Nontypeable Haemophilus influenzae (NTHI), a common colonizer of lungs of patients with chronic obstructive pulmonary disease (COPD), can enhance expression of the cellular receptor intercellular adhesion molecule 1 (ICAM-1), which in turn can be used by major group human rhinoviruses (HRVs) for attachment. Here, we evaluated the effect of NTHI-induced up-regulation of ICAM-1 on viral replication and inflammatory responses toward different respiratory viruses. Therefore, human bronchial epithelial cells were pretreated with heat-inactivated NTHI (hi-NTHI) and subsequently infected with either HRV16 (major group), HRV1B (minor group), or respiratory syncytial virus (RSV). Pretreatment with hi-NTHI significantly up-regulated ICAM-1 in BEAS-2B cells and primary bronchial epithelial cells. Concomitantly, release of infectious HRV16 particles was increased in cells pretreated with hi-NTHI. Pretreatment with hi-NTHI also caused a significant increase in HRV16 RNA, whereas replication of HRV1B and RSV were increased to a far lesser extent and only at later time points. Interestingly, release of IL-6 and IL-8 after RSV, but not HRV, infection was synergistically increased in hi-NTHI-pretreated BEAS-2B cells. In summary, exposure to hi-NTHI significantly enhanced sensitivity toward HRV16 but not HRV1B or RSV, probably through ICAM-1 up-regulation. Furthermore, hi-NTHI pretreatment may enhance the inflammatory response to RSV infection, suggesting that preexisting bacterial infections might exaggerate inflammation during secondary viral infection.
authors.affiliation: Departments of *Medical Microbiology and Respiratory Medicine, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Fahad
authors.initials: F
authors.lastname: Gulraiz
authors.affiliation: Departments of *Medical Microbiology and Respiratory Medicine, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Carla
authors.initials: C
authors.lastname: Bellinghausen
authors.affiliation: Departments of *Medical Microbiology and Respiratory Medicine, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Cathrien A
authors.initials: CA
authors.lastname: Bruggeman
authors.affiliation: Departments of *Medical Microbiology and Respiratory Medicine, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands f.stassen@maastrichtuniversity.nl.
authors.forename: Frank R
authors.initials: FR
authors.lastname: Stassen
mesh_terms: D001980:Bronchi / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D004198:Disease Susceptibility; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D006192:Haemophilus Infections / Q000150:complications* / Q000382:microbiology; D006193:Haemophilus influenzae / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000502:physiology; D014779:Virus Replication
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D012367:RNA, Viral; D018799:Intercellular Adhesion Molecule-1
keywords: CD54; HRV; NTHI; RSV; coinfection