Infect Immun. 2016 Feb 29. pii: IAI.01504-15. [Epub ahead of print]
Shen P1, Morissette MC2, Vanderstocken G2, Gao Y2, Hassan M3, Roos A4, Thayaparan D5, Merlano M6, Dorrington MG1, Nikota JK1, Bauer CM7,Kwiecien JM8, Labiris R9, Bowdish DM2, Stevenson CS7, Stämpfli MR10.
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.
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PMID: 26930709 [PubMed - as supplied by publisher]