Cessation from smoking improves innate host defense and clearance of experimentally inoculated nasal S. aureus

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