title: Cigarette Smoke Attenuates the Nasal Host Response to Streptococcus pneumoniae and Predisposes to Invasive Pneumococcal Disease in Mice.
abstract: Streptococcus pneumoniae is a leading cause of invasive bacterial infections, with nasal colonization an important first step in disease. While cigarette smoking is a strong risk factor for invasive pneumococcal disease, the 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 bacteremia and meningitis without prior lung infection. Mechanistically, deficiency in interleukin 1α (IL-1α) or platelet-activating factor receptor (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 remains high worldwide, these findings are relevant to the continued efforts to reduce the invasive pneumococcal disease burden.
authors.affiliation: Medical Sciences Graduate Program, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Pamela
authors.initials: P
authors.lastname: Shen
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Mathieu C
authors.initials: MC
authors.lastname: Morissette
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Gilles
authors.initials: G
authors.lastname: Vanderstocken
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Honours Biology and Pharmacology Co-op Program, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Hassan
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.|Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Abraham
authors.initials: A
authors.lastname: Roos
authors.affiliation: Honours Molecular Biology and Genetics Co-op Program, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Danya
authors.initials: D
authors.lastname: Thayaparan
authors.affiliation: Honours Bachelor of Health Sciences Undergraduate Program, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Maria
authors.initials: M
authors.lastname: Merlano
authors.affiliation: Medical Sciences Graduate Program, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Dorrington
authors.affiliation: Medical Sciences Graduate Program, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jake K
authors.initials: JK
authors.lastname: Nikota
authors.affiliation: Hoffmann-La Roche, pRED, Pharma Research and Early Development, DTA Inflammation, Nutley, New Jersey, USA.
authors.forename: Carla M T
authors.initials: CMT
authors.lastname: Bauer
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.|Department of Neurosurgery and Paediatric Neurosurgery, Medical University of Lublin, Lublin, Poland.
authors.forename: Jacek M
authors.initials: JM
authors.lastname: Kwiecien
authors.affiliation: Department of Medicine, Division of Respirology, McMaster University, Hamilton, Ontario, Canada.|Department of Medicine, Firestone Institute for Respiratory Health at St. Joseph's Healthcare, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Renee
authors.initials: R
authors.lastname: Labiris
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Dawn M E
authors.initials: DME
authors.lastname: Bowdish
authors.affiliation: Hoffmann-La Roche, pRED, Pharma Research and Early Development, DTA Inflammation, Nutley, New Jersey, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Stevenson
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada stampfli@mcmaster.ca.|Department of Medicine, Firestone Institute for Respiratory Health at St. Joseph's Healthcare, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Stämpfli
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000382:microbiology / Q000517:prevention & control; D002353:Carrier State / Q000276:immunology* / Q000517:prevention & control; D004195:Disease Models, Animal; D060467:Disease Resistance; D008586:Meningitis, Pneumococcal / Q000382:microbiology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009297:Nasal Mucosa / Q000276:immunology / Q000382:microbiology*; D009504:Neutrophils / Q000276:immunology; D011008:Pneumococcal Infections / Q000276:immunology* / Q000517:prevention & control; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D013296:Streptococcus pneumoniae / Q000254:growth & development* / Q000276:immunology
chemical_list: D012906:Smoke