LSC Abstract – Synergistic pro-inflammatory effects of Haemophilus influenzae/RSV co-infections on respiratory epithelial cells

Infection with one microorganism can influence secondary infections with other, unrelated pathogens by for example, breaching mucosal barriers or altering the host9s immune response. While this topic has been studied in detail for respiratory viral infections facilitating bacterial superinfections, the reverse order is less well understood. In order to investigate how the presence of bacteria affects a secondary viral infection, bronchial epithelial cells (BEAS-2B) were exposed to heat-inactivated (hi) suspensions of nontypeable H. influenzae (NTHI), Pseudomonas aeruginosa or Streptococcus pneumoniae and subsequently infected with Respiratory Syncytial Virus (RSV). Response to infection was measured by monitoring cytokine release and viral replication. Exposure to bacteria and viral infection independently caused the release of the inflammatory cytokines IL-6 and IL-8 by BEAS-2B cells. When cells were first exposed to hi-NTHI and then infected with RSV, release of both cytokines was synergistically enhanced. Seventy-two hours after viral infection, measured cytokine levels exceeded a purely additive effect of the individual pathogens by 120% (IL-6) and 150% (IL-8), respectively. This exaggerated response was not linked to viral replication and was to such extent only seen for hi-NTHI but none of the other pathogens. Our data suggest that bacteria can contribute to the severity of secondary viral infections in a pathogen-specific manner. Considering the substantial proportion of patients with chronic lung diseases whose lungs are colonized with bacteria, it seems likely that such colonization can affect their susceptibility and response to secondary viral infections.