Exposure to common respiratory bacteria alters the airway epithelial response to subsequent viral infection.
Colonization of the airways with potential pathogenic bacteria is observed in a number of chronic respiratory diseases, such as COPD or cystic fibrosis. Infections with respiratory viruses are known triggers of exacerbations of these diseases. We here investigated if pre-exposure to bacteria alters the response of lung epithelial cells to subsequent viral infection.



Bronchial epithelial cells (BEAS-2B cells and primary bronchial epithelial cells) were exposed to heat-inactivated Haemophilus influenzae, Pseudomonas aeruginosa or Streptococcus pneumoniae and subsequently infected with respiratory syncytial virus (RSV), type 2 human adenovirus or influenza B. Levels of pro-inflammatory cytokines, viral replication and expression of pattern recognition receptors were determined in culture supernatants and/or cell lysates.



Exposure of BEAS-2B cells to H. influenzae before and during RSV-infection synergistically increased the release of IL-6 (increase above calculated additive effect at 72 h: 56 % ± 3 %, mean ± SEM) and IL-8 (53 % ± 12 %). This effect was sustained even when bacteria were washed away before viral infection and was neither associated with enhanced viral replication, nor linked to increased expression of key pattern recognition receptors. P. aeruginosa enhanced the release of inflammatory cytokines to a similar extent, yet only if bacteria were also present during viral infection. S. pneumoniae did not enhance RSV-induced cytokine release. Surprisingly, adenovirus infection significantly reduced IL-6 release in cells exposed to either of the three tested bacterial strains by on average more than 50 %. Infection with influenza B on the other hand did not affect cytokine production in BEAS-2B cells exposed to the different bacterial strains.



Pre-exposure of epithelial cells to bacteria alters the response to subsequent viral infection depending on the types of pathogen involved. These findings highlight the complexity of microbiome interactions in the airways, possibly contributing to the susceptibility to exacerbations and the natural course of airway diseases.
Department of Medical Microbiology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands.|Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
Carla
C
Bellinghausen
Department of Medical Microbiology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands.|Department of Cell Biology and Immunology, University of North Texas Health Science Center (UNT Health Science Center), Fort Worth, TX, USA.
Fahad
F
Gulraiz
Department of Medical Microbiology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands.
Alexandra C A
AC
Heinzmann
Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
Mieke A
MA
Dentener
Department of Medical Microbiology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands.|Department of Medical Microbiology & Infection Control, VU University Medical Center, Amsterdam, The Netherlands.
Paul H M
PH
Savelkoul
Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
Emiel F
EF
Wouters
Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
Gernot G
GG
Rohde
Department of Medical Microbiology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands. f.stassen@maastrichtuniversity.nl.|, P.O. Box 5800, 6202AZ, Maastricht, The Netherlands. f.stassen@maastrichtuniversity.nl.
Frank R
FR
Stassen
D000256:Adenoviridae / Q000472:pathogenicity; D000818:Animals; D001419:Bacteria / Q000276:immunology / Q000472:pathogenicity*; D002522:Chlorocebus aethiops; D060085:Coinfection; D016207:Cytokines / Q000378:metabolism; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology* / Q000821:virology*; D006193:Haemophilus influenzae / Q000472:pathogenicity; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D009981:Influenza B virus / Q000472:pathogenicity; D008168:Lung / Q000378:metabolism / Q000382:microbiology* / Q000821:virology*; D061985:Madin Darby Canine Kidney Cells; D061251:Primary Cell Culture; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity; D012136:Respiratory Syncytial Viruses / Q000472:pathogenicity; D012141:Respiratory Tract Infections / Q000378:metabolism / Q000382:microbiology* / Q000821:virology*; D013296:Streptococcus pneumoniae / Q000472:pathogenicity; D013997:Time Factors; D014709:Vero Cells; D014780:Viruses / Q000276:immunology / Q000472:pathogenicity*
D016207:Cytokines; D018836:Inflammation Mediators
Bacterial-viral co-infection; Inflammation; Polymicrobial infection