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Updated: Jul 22, 2025
A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
Published on: February 28, 2019
γδ T cell-intrinsic IL-1R promotes survival during Staphylococcus aureus bacteremia
Yu Wang1, Michael Z Ahmadi1, Dustin A Dikeman1
1Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Abstract:
Staphylococcus aureus is a leading cause of bacteremia, further complicated by the emergence of antibiotic-resistant strains such as methicillin-resistant S. aureus (MRSA). A better understanding of host defense mechanisms is needed for the development of host-directed therapies as an alternative approach to antibiotics. The levels of IL-1, IL-17, and TNF-α cytokines in circulation have been associated with predictive outcomes in patients with S. aureus bacteremia. However, their causative role in survival and the cell types involved in these responses during bacteremia is not entirely clear. Using a mouse model of S. aureus bacteremia, we demonstrated that IL-17A/F and TNF-α had no significant impact on survival, whereas IL-1R signaling was critical for survival during S. aureus bacteremia. Furthermore, we identified that T cells, but not neutrophils, monocytes/macrophages, or endothelial cells were the crucial cell type for IL-1R-mediated survival against S. aureus bacteremia. Finally, we determined that the expression of IL-1R on γδ T cell, but not CD4+ or CD8+ T cells was responsible for survival against the S. aureus bacteremia. Taken together, we uncovered a role for IL-1R, but not IL-17A/F and TNF-α in protection against S. aureus bacteremia. Importantly, γδ T cell-intrinsic expression of IL-1R was crucial for survival, but not on other immune cells or endothelial cells. These findings reveal potential cellular and immunological targets for host-directed therapies for improved outcomes against S. aureus bacteremia.
Insights
Interleukin-1 receptor (IL-1R) signaling is crucial for survival during Staphylococcus aureus bacteremia. Gamma delta T cells expressing IL-1R are key to this protective response, offering potential targets for new therapies.
Area of Science:
- Immunology
- Infectious Diseases
- Microbiology
Background:
- Staphylococcus aureus bacteremia, including MRSA, requires novel therapies beyond antibiotics.
- Understanding host defense mechanisms is vital for developing host-directed treatments.
- While IL-1, IL-17, and TNF-α are linked to outcomes, their specific roles in S. aureus bacteremia are unclear.
Purpose of the Study:
- To investigate the roles of IL-1R, IL-17A/F, and TNF-α in host survival during S. aureus bacteremia.
- To identify the specific immune cell types mediating IL-1R-dependent protection.
- To determine the precise T cell subset responsible for IL-1R-mediated survival.
Main Methods:
- Utilized a mouse model of Staphylococcus aureus bacteremia.
- Assessed the impact of IL-1R, IL-17A/F, and TNF-α on survival rates.
- Employed cell-specific knockout strategies to identify critical immune cell populations.
- Analyzed IL-1R expression on different T cell subsets (γδ T cells, CD4+, CD8+ T cells).
Main Results:
- IL-17A/F and TNF-α did not significantly affect survival in S. aureus bacteremia.
- IL-1R signaling was essential for host survival.
- T cells, not neutrophils, monocytes/macrophages, or endothelial cells, were critical for IL-1R-mediated protection.
- IL-1R expression on γδ T cells, but not other T cell types, was responsible for survival.
Conclusions:
- IL-1R signaling, particularly on γδ T cells, plays a critical protective role in Staphylococcus aureus bacteremia.
- IL-17A/F and TNF-α are not major determinants of survival in this model.
- γδ T cell-intrinsic IL-1R is a potential therapeutic target for S. aureus infections.
- Findings highlight a specific immune pathway for developing novel host-directed therapies.
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