School of Medicine and Health Sciences Poster Presentations

Title

Delayed onset of IL-17A/F-mediated protective immunity against community-acquired MRSA skin infection

Document Type

Poster

Keywords

Skin; Infection; Innate immunity

Publication Date

Spring 2017

Abstract

The high recurrence rate of S. aureus skin and soft tissue (SSTI) caused by community-acquired methicillin-resistant S. aureus (CA-MRSA), suggests that long-lasting immunity is not generated in many individuals. If immune-based therapies are to provide an alternative to antibiotics, understanding the key immune responses that promote protection against CA-MRSA is essential. Previous reports in mice found that IL-17A/F production by γδ T cells mediated early neutrophil recruitment and host defense (within the first 24 hours) against a skin challenge with a methicillin-sensitive S. aureus laboratory strain. To elucidate the role of IL-17A/F in host defense against a CA-MRSA SSTI, IL-17A/F-deficient and wt mice were inoculated intradermally with a bioluminescent derivative of a CA-MRSA clinical isolate (USA300 LAC). Remarkably, IL-17A/F-deficient mice did not have an early immune defect, but rather they developed significantly larger lesions and increased bacterial burden compared with wt mice at days 7 and 10 following infection. Using IL-17A/F tdTomato/GFP fluorescent dual reporter mice, IL-17A/F cytokine expression peaked at days 7 and 10, corresponding with the timing of the immune defect in the IL-17A/F-deficient mice. The major IL-17A/F-producing cells in the skin and draining lymph nodes were γδ T cells. Additionally, TNFα mRNA and protein levels were significantly decreased in the affected skin at day 7 in IL-17A/F-deficient mice compared with wt mice. Taken together, in response to a CA-MRSA SSTI, IL-17A/F (and TNFα) contributed to host defense at later time points during the infectious course than anticipated, suggesting that the delay in the protective immune response might be due to the increased virulence of CA-MRSA isolates.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Open Access

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Comments

Poster to be presented at GW Annual Research Days 2017.

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Delayed onset of IL-17A/F-mediated protective immunity against community-acquired MRSA skin infection

The high recurrence rate of S. aureus skin and soft tissue (SSTI) caused by community-acquired methicillin-resistant S. aureus (CA-MRSA), suggests that long-lasting immunity is not generated in many individuals. If immune-based therapies are to provide an alternative to antibiotics, understanding the key immune responses that promote protection against CA-MRSA is essential. Previous reports in mice found that IL-17A/F production by γδ T cells mediated early neutrophil recruitment and host defense (within the first 24 hours) against a skin challenge with a methicillin-sensitive S. aureus laboratory strain. To elucidate the role of IL-17A/F in host defense against a CA-MRSA SSTI, IL-17A/F-deficient and wt mice were inoculated intradermally with a bioluminescent derivative of a CA-MRSA clinical isolate (USA300 LAC). Remarkably, IL-17A/F-deficient mice did not have an early immune defect, but rather they developed significantly larger lesions and increased bacterial burden compared with wt mice at days 7 and 10 following infection. Using IL-17A/F tdTomato/GFP fluorescent dual reporter mice, IL-17A/F cytokine expression peaked at days 7 and 10, corresponding with the timing of the immune defect in the IL-17A/F-deficient mice. The major IL-17A/F-producing cells in the skin and draining lymph nodes were γδ T cells. Additionally, TNFα mRNA and protein levels were significantly decreased in the affected skin at day 7 in IL-17A/F-deficient mice compared with wt mice. Taken together, in response to a CA-MRSA SSTI, IL-17A/F (and TNFα) contributed to host defense at later time points during the infectious course than anticipated, suggesting that the delay in the protective immune response might be due to the increased virulence of CA-MRSA isolates.