title: Chronic ethanol feeding increases the severity of Staphylococcus aureus skin infections by altering local host defenses.
abstract: Alcoholics are at increased risk of Staphylococcus aureus skin infection and serious sequelae, such as bacteremia and death. Despite the association between alcoholism and severe S. aureus skin infection, the impact of EtOH on anti-S. aureus cutaneous immunity has not been investigated in a model of chronic EtOH exposure. To test the hypothesis that EtOH enhances the severity of S. aureus skin infection, mice were fed EtOH for ≥12 weeks via the Meadows-Cook model of alcoholism and inoculated with S. aureus following epidermal abrasion. Evidence of exacerbated staphylococcal disease in EtOH-fed mice included: skin lesions that were larger and contained more organisms, greater weight loss, and increased bacterial dissemination. Infected EtOH-fed mice demonstrated poor maintenance and induction of PMN responses in skin and draining LNs, respectively. Additionally, altered PMN dynamics in the skin of these mice corresponded with reduced production of IL-23 and IL-1β by CD11b(+) myeloid cells and IL-17 production by γδ T cells, with the latter defect occurring in the draining LNs as well. In addition, IL-17 restoration attenuated S. aureus-induced dermatopathology and improved bacterial clearance defects in EtOH-fed mice. Taken together, the findings show, in a novel model system, that the EtOH-induced increase in S. aureus-related injury/illness corresponds with defects in the IL-23/IL-17 inflammatory axis and poor PMN accumulation at the site of infection and draining LNs. These findings offer new information about the impact of EtOH on cutaneous host-defense pathways and provide a potential mechanism explaining why alcoholics are predisposed to S. aureus skin infection.
authors.affiliation: Departments of *Pathology and Microbiology and Interdisciplinary Graduate Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
authors.forename: Corey P
authors.initials: CP
authors.lastname: Parlet
authors.affiliation: Departments of *Pathology and Microbiology and Interdisciplinary Graduate Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Kavanaugh
authors.affiliation: Departments of *Pathology and Microbiology and Interdisciplinary Graduate Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Horswill
authors.affiliation: Departments of *Pathology and Microbiology and Interdisciplinary Graduate Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA annette-schlueter@uiowa.edu.
authors.forename: Annette J
authors.initials: AJ
authors.lastname: Schlueter
mesh_terms: D000437:Alcoholism / Q000276:immunology*; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D016470:Bacteremia / Q000209:etiology; D058491:Bacterial Load; D054804:Cathelicidins / Q000096:biosynthesis; D004198:Disease Susceptibility; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D016867:Immunocompromised Host; D020381:Interleukin-17 / Q000096:biosynthesis / Q000627:therapeutic use; D053583:Interleukin-1beta / Q000096:biosynthesis; D053759:Interleukin-23 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D020556:Neutrophil Infiltration; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011994:Recombinant Proteins / Q000627:therapeutic use; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013047:Specific Pathogen-Free Organisms; D013207:Staphylococcal Skin Infections / Q000188:drug therapy / Q000209:etiology / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000276:immunology / Q000302:isolation & purification; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis; D015431:Weight Loss
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D020381:Interleukin-17; D053583:Interleukin-1beta; D053759:Interleukin-23; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011994:Recombinant Proteins; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D000431:Ethanol
keywords: IL-17; PMNs; T cells