Haemophilus influenzae increases the susceptibility and inflammatory response of airway epithelial cells to viral infections

FASEB J. 2015 Mar;29(3):849-58. doi: 10.1096/fj.14-254359. Epub 2014 Nov 19.


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.

Keywords: CD54; HRV; NTHI; RSV; coinfection.

MeSH terms

  • Bronchi / immunology*
  • Bronchi / metabolism
  • Bronchi / virology
  • Cells, Cultured
  • Disease Susceptibility*
  • Epithelial Cells / immunology*
  • Epithelial Cells / metabolism
  • Epithelial Cells / virology
  • Haemophilus Infections / complications*
  • Haemophilus Infections / microbiology
  • Haemophilus influenzae / physiology*
  • Humans
  • Immunoblotting
  • Inflammation / immunology*
  • Inflammation / metabolism
  • Inflammation / virology
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Polymerase Chain Reaction
  • RNA, Viral / genetics
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Infections / metabolism
  • Respiratory Syncytial Virus Infections / virology
  • Respiratory Syncytial Viruses / physiology
  • Virus Replication


  • Interleukin-6
  • Interleukin-8
  • RNA, Viral
  • Intercellular Adhesion Molecule-1