Cigarette smoke attenuates the nasal host response to Streptococcus pneumoniae and predisposes to invasive pneumococcal disease in mice.

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Streptococcus pneumoniae is a leading cause of invasive bacterial infections, with nasal colonization an important first step for disease. While cigarette smoking is a strong risk factor for invasive pneumococcal disease, underlying mechanisms remain unknown. This is partly due to a lack of clinically relevant animal models investigating nasal pneumococcal colonization in the context of cigarette smoke exposure. We present a model of nasal pneumococcal colonization in cigarette smoke-exposed mice and document, for the first time, that cigarette smoke predisposes to invasive pneumococcal infection and mortality in an animal model. Cigarette smoke increased the risk of bacteraemia and meningitis without prior lung infection. Mechanistically, deficiency in IL-1α or PAFR, an important host receptor thought to bind and facilitate pneumococcal invasiveness, did not rescue cigarette smoke-exposed mice from invasive pneumococcal disease. Importantly, we observed cigarette smoke to attenuate nasal inflammatory mediator expression, particularly that of neutrophil recruiting chemokines, normally elicited by pneumococcal colonization. Smoking cessation during nasal pneumococcal colonization rescued nasal neutrophil recruitment and prevented invasive disease in mice. We propose that cigarette smoke predisposes to invasive pneumococcal disease by suppressing inflammatory processes of the upper respiratory tract. Given that smoking prevalence remain high worldwide, these findings are relevant to the continued efforts to reduce invasive pneumococcal disease burden.


  • Pamela Shen
  • Mathieu C Morissette
  • Gilles Vanderstocken
  • Yang Gao
  • Muhammad Hassan
  • Abraham Roos
  • Danya Thayaparan
  • Maria Merlano
  • Michael G Dorrington
  • Jake K Nikota
  • Carla Mt Bauer
  • Jacek M Kwiecien
  • Renee Labiris
  • Dawn Me Bowdish
  • Christopher S Stevenson
  • Martin R Stämpfli
Enheter & grupper
Externa organisationer
  • McMaster University
  • F. Hoffmann-La Roche AG

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Immunologi inom det medicinska området
Sidor (från-till)1536-1547
TidskriftInfection and Immunity
Utgåva nummer5
Tidigt onlinedatum2016 feb 29
StatusPublished - 2016
Peer review utfördJa