title: Impact of Staphylococcus aureus USA300 Colonization and Skin Infections on Systemic Immune Responses in Humans.
abstract: Staphylococcus aureus is both a commensal and a pathogen, and USA300, a strain that is usually methicillin-resistant but can sometimes be methicillin-susceptible, has been causing skin and soft tissue infections (SSTIs) in epidemic proportions among otherwise healthy individuals. Although many people are colonized with S. aureus strains, including some with USA300, few of these colonized individuals develop SSTIs. This prompts the hypothesis that infections may develop in individuals with somewhat reduced innate and/or adaptive immune responses to S. aureus, either because prior S. aureus colonization has dampened such responses selectively, or because of more globally reduced immune reactivity. In this study, we analyzed the S. aureus colonization status and PBMC responses to innate and adaptive stimuli in 72 patients with SSTIs and 143 uninfected demographically matched controls. Contrary to the hypothesis formulated, PBMCs from infected patients obtained at the time of infection displayed enhanced innate cytokine production upon restimulation compared with PBMCs from controls, a difference that disappeared after infection resolution. Notably, PBMCs from patients infected with a documented USA300 SSTI displayed greater innate cytokine production than did those from patients infected with documented non-USA300 genotypes. Moreover, colonization with USA300 in infected patients, regardless of their infecting strain, correlated with increased production of IL-10, IL-17A, and IL-22 compared with patients colonized with non-USA300 subtypes. Thus, our results demonstrate that infected patients associated with USA300 either as an infecting strain, or as a colonizing strain, have systemic immune responses of greater magnitude than do those associated with other S. aureus subtypes.
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637; malegre@midway.uchicago.edu.
authors.forename: Maria-Luisa
authors.identifier: 0000-0001-5707-6194
authors.initials: ML
authors.lastname: Alegre
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637;
authors.forename: Luqiu
authors.identifier: 0000-0001-8537-6071
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637; Department of Pediatrics, University of Chicago, Chicago, IL 60637;
authors.forename: Michael Z
authors.identifier: 0000-0002-1926-7800
authors.initials: MZ
authors.lastname: David
authors.affiliation: University of Pennsylvania, Philadelphia, PA 19104; and.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bartman
authors.affiliation: Department of Pediatrics, University of Chicago, Chicago, IL 60637;
authors.forename: Susan
authors.initials: S
authors.lastname: Boyle-Vavra
authors.affiliation: Department of Pediatrics, University of Chicago, Chicago, IL 60637;
authors.forename: Neha
authors.initials: N
authors.lastname: Kumar
authors.affiliation: Department of Surgery, University of Chicago, Chicago, IL 60637.
authors.forename: Anita S
authors.initials: AS
authors.lastname: Chong
authors.affiliation: Department of Pediatrics, University of Chicago, Chicago, IL 60637; Department of Surgery, University of Chicago, Chicago, IL 60637.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Daum
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002981:Clindamycin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D013207:Staphylococcal Skin Infections / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000235:genetics / Q000276:immunology; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D002981:Clindamycin; D015662:Trimethoprim, Sulfamethoxazole Drug Combination