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

F. Gulraiz, C. Bellinghausen, C.A. Bruggeman, F.R. Stassen

Research output: Contribution to journalArticleAcademicpeer-review

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.
Original languageEnglish
Pages (from-to)849-858
Number of pages10
JournalFaseb Journal
Volume29
Issue number3
DOIs
Publication statusPublished - Mar 2015

Keywords

  • NTHI
  • HRV
  • RSV
  • coinfection
  • CD54
  • OBSTRUCTIVE PULMONARY-DISEASE
  • INTERCELLULAR-ADHESION MOLECULE-1
  • RESPIRATORY SYNCYTIAL VIRUS
  • RHINOVIRUS INFECTION
  • ICAM-1 EXPRESSION
  • STREPTOCOCCUS-PNEUMONIAE
  • ALVEOLAR MACROPHAGES
  • IMMUNE-RESPONSES
  • CYSTIC-FIBROSIS
  • RT-PCR

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