title: Host innate inflammatory factors and staphylococcal protein A influence the duration of human Staphylococcus aureus nasal carriage.
abstract: Human Staphylococcus aureus (SA) nasal carriage provides a reservoir for the dissemination of infectious strains; however, factors regulating the establishment and persistence of nasal colonization are mostly unknown. We measured carriage duration and nasal fluid inflammatory markers after nasally inoculating healthy participants with their previously isolated SA strains. Out of 15 studies, 10 resulted in rapid clearance (9±6 days) that corresponded with upregulated chemokines, growth factors, and predominantly Th1-type cytokines, but not interleukin (IL)-17. Nasal SA persistence corresponded with elevated baseline levels of macrophage inflammatory protein-1β, IL-1β, and IL-6, no induction of inflammatory factors after inoculation, and decreased IL-1 receptor antagonist/IL-1β ratio. SA-expressed staphylococcal protein A (SpA) levels correlated positively with carriage duration. Competitive inoculation studies revealed that isogenic SpA knockout (ΔSpA) strains were cleared faster than wild type only in participants with upregulated inflammatory markers after inoculation. The remaining participants did not mount an inflammatory response and did not clear either strain. ΔSpA strains demonstrated lower growth rates in carrier nasal fluids and lower survival rates when incubated with neutrophils. Collectively, the presented studies identify innate immune effectors that cooperatively modulate nasal carriage duration, and confirm SpA as a bacterial codeterminant of SA nasal carriage.
authors.affiliation: Laboratory of Innate Host Defense, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Cole
authors.affiliation: Laboratory of Innate Host Defense, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, USA.
authors.forename: G
authors.initials: G
authors.lastname: Muthukrishnan
authors.affiliation: Laboratory of Innate Host Defense, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, USA.
authors.forename: C
authors.initials: C
authors.lastname: Chong
authors.affiliation: Laboratory of Innate Host Defense, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, USA.
authors.forename: A
authors.initials: A
authors.lastname: Beavis
authors.affiliation: Laboratory of Innate Host Defense, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Eade
authors.affiliation: Laboratory of Innate Host Defense, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Wood
authors.affiliation: Health Services, University of Central Florida, Orlando, Florida, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Deichen
authors.affiliation: Laboratory of Innate Host Defense, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Cole
mesh_terms: D001422:Bacterial Adhesion; D002353:Carrier State; D016207:Cytokines / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D050296:Microbial Viability / Q000276:immunology; D009154:Mutation; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D013203:Staphylococcal Infections / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology*; D013205:Staphylococcal Protein A / Q000235:genetics / Q000276:immunology*; D013211:Staphylococcus aureus / Q000145:classification / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D013205:Staphylococcal Protein A
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