Chronic ethanol feeding increases the severity of Staphylococcus aureus skin infections by altering local host defenses

Corey P Parlet; Jeffrey S Kavanaugh; Alexander R Horswill; Annette J Schlueter

doi:10.1189/jlb.4A0214-092R

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Chronic ethanol feeding increases the severity of Staphylococcus aureus skin infections by altering local host defenses

Journal article

Open access

Peer reviewed

Chronic ethanol feeding increases the severity of Staphylococcus aureus skin infections by altering local host defenses

Corey P Parlet, Jeffrey S Kavanaugh, Alexander R Horswill and Annette J Schlueter

Journal of leukocyte biology, Vol.97(4), pp.769-778

04/2015

DOI: 10.1189/jlb.4A0214-092R

PMCID: PMC4370047

PMID: 25605871

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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.

Recombinant Proteins - therapeutic use

T-Lymphocyte Subsets - immunology

Ethanol - toxicity

Skin - metabolism

Neutrophil Infiltration

Hypersensitivity, Delayed - immunology

Staphylococcal Skin Infections - drug therapy

Myeloid Cells - immunology

Staphylococcal Skin Infections - immunology

Bacteremia - etiology

Female

Interleukin-1beta - biosynthesis

Alcoholism - immunology

Skin - pathology

Skin - immunology

Cathelicidins - biosynthesis

Disease Susceptibility

Specific Pathogen-Free Organisms

Staphylococcus aureus - isolation & purification

Antimicrobial Cationic Peptides

Mice, Inbred C57BL

Lymph Nodes - metabolism

Bacterial Load

Interleukin-17 - biosynthesis

Interleukin-17 - therapeutic use

Staphylococcal Skin Infections - pathology

Toll-Like Receptor 2 - biosynthesis

Animals

Staphylococcal Skin Infections - etiology

T-Lymphocyte Subsets - metabolism

Weight Loss

Interleukin-23 - biosynthesis

Myeloid Cells - metabolism

Receptors, Antigen, T-Cell, gamma-delta

Staphylococcus aureus - immunology

Mice

Immunocompromised Host

Staphylococcal Skin Infections - microbiology

Details

Title: Subtitle: Chronic ethanol feeding increases the severity of Staphylococcus aureus skin infections by altering local host defenses
Creators: Corey P Parlet - Departments of Pathology and Microbiology and Interdisciplinary Graduate Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Jeffrey S Kavanaugh - Departments of Pathology and Microbiology and Interdisciplinary Graduate Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Alexander R Horswill - Departments of Pathology and Microbiology and Interdisciplinary Graduate Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Annette J Schlueter - 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
Resource Type: Journal article
Publication Details: Journal of leukocyte biology, Vol.97(4), pp.769-778
Publisher: United States
DOI: 10.1189/jlb.4A0214-092R
PMID: 25605871
PMCID: PMC4370047
ISSN: 0741-5400
eISSN: 1938-3673
Grant note: T32 AI007343 / NIAID NIH HHS R01 AA019568 / NIAAA NIH HHS
Language: English
Date published: 04/2015
Academic Unit: Microbiology and Immunology; Pathology
Record Identifier: 9984047763702771

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