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

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
  • 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
Organisations
External organisations
  • McMaster University
  • F. Hoffmann-La Roche AG
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area
Original languageEnglish
Pages (from-to)1536-1547
JournalInfection and Immunity
Volume84
Issue number5
Early online date2016 Feb 29
Publication statusPublished - 2016
Publication categoryResearch
Peer-reviewedYes