Cessation from Smoking Improves Innate Host Defense and Clearance of Experimentally Inoculated Nasal Staphylococcus aureus

Abstract

<i>Staphylococcus aureus</i> nasal carriage is transient in most humans and usually benign, but dissemination of <i>S. aureus</i> to extranasal sites causes the majority of clinical infections, and <i>S. aureus</i> is a major cause of serious infections in the United States. A better understanding of innate nasal decolonization mechanisms is urgently needed, as are relevant models for studying <i>S. aureus</i> clearance. Here, we screened a population of healthy smokers for nasal <i>S. aureus</i> carriage and compared the participants' abilities to clear experimentally applied nasal <i>S. aureus</i> before and after completion of a smoking cessation program. We determined that cigarette smoking increases the mean nasal <i>S. aureus</i> load (2.6 × 10⁴ CFU/swab) compared to the load observed in healthy nonsmokers (1.7 × 10³ CFU/swab) and might increase the rate of <i>S. aureus</i> nasal carriage in otherwise-healthy adults: 22 of 99 smokers carried <i>S. aureus</i> at the screening visit, while only 4 of 30 nonsmokers screened positive during the same time period. Only 6 of 19 experimental inoculation studies in active smokers resulted in <i>S. aureus</i> clearance within the month of follow-up, while in the cessation group, 6 of 9 subjects cleared nasal <i>S. aureus</i> and carriage duration averaged 21 ± 4 days. Smoking cessation associated with enhanced expression of <i>S. aureus</i>-associated interleukin-1β (IL-1β) and granulocyte colony-stimulating factor (G-CSF) in nasal fluids. Participants who failed to clear <i>S. aureus</i> exhibited a higher nasal <i>S. aureus</i> load and elevated nasal interleukin-1 receptor antagonist (IL-1RA) expression at the preexperiment study visits. We conclude that smokers exhibit higher <i>S. aureus</i> loads than nonsmokers and that innate immune pathways, including G-CSF expression and signaling through the IL-1 axis, are important mediators of nasal <i>S. aureus</i> clearance.