γδ T cell-intrinsic IL-1R promotes survival during Staphylococcus aureus bacteremia.

Autor:	Wang Y; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, United States., Ahmadi MZ; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, United States., Dikeman DA; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, United States., Youn C; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, United States., Archer NK; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Jul 07; Vol. 14, pp. 1171934. Date of Electronic Publication: 2023 Jul 07 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1171934
Abstrakt:	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. Competing Interests: NA has received previous grant support from Pfizer and Boehringer Ingelheim and has been a paid consultant for Janssen Pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest. (Copyright © 2023 Wang, Ahmadi, Dikeman, Youn and Archer.)
Databáze:	MEDLINE
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