High expression of interleukin-18 receptor alpha correlates with severe respiratory viral disease and defines T cells with reduced cytotoxic signatures
- Author(s)
- Cabug, AF; Crawford, JC; McQuilten, HA; Foo, IJH; Allen, LF; Gebregzabher, D; Mettelman, RC; Novak, T; Chou, J; Rowntree, LC; Hagen, RR; Thomson, AJ; Martin, GE; Gilbertson, B; Souter, MNT; James, F; Goodall, E; Rizzetto, S; Flerlage, T; Jia, X; Van de Velde, LA; Chang, SY; Luciani, F; Thwaites, RS; Trubiano, JA; Kotsimbos, TC; Cheng, AC; Randolph, AG; Thomas, PG; Xu, J; Wang, Z; Nguyen, THO; Chua, BY; Kedzierski, L; Kedzierska, K;
- Journal Title
- Nature Communications
- Publication Type
- Research article
- Abstract
- Hyperactivated immunity underpins severe outcomes of respiratory viral infections, yet specific immune perturbations are ill-defined. Our recent findings identified OLAH (oleoyl-ACP-hydrolase) as a driver of life-threatening viral diseases. In the same patient cohorts, we now identify the gene encoding IL-18Rα chain (IL18R1), as being highly expressed in life-threatening influenza, COVID-19, RSV and multisystem inflammatory syndrome in children (MIS-C) and demonstrate markedly elevated surface protein IL-18Rα expression on CD8 T cells in these infections. Using a mouse model of severe influenza, we further show that high IL-18Rα expression on effector T cells is associated with increased disease severity. We find that IL-18Rα expression on CD8 T cells is inversely associated with cytotoxicity-related genes, including granzyme A, granzyme B, perforin, Eomes, and KLRG-1. Our study demonstrates that IL-18Rα is associated with severe and fatal respiratory disease outcomes and proposes the use of IL-18Rα as a potential biomarker for severe respiratory viral disease.
- Keywords
- Animals; *COVID-19/immunology/genetics/complications; Humans; Mice; *CD8-Positive T-Lymphocytes/immunology/metabolism; *Interleukin-18 Receptor alpha Subunit/genetics/metabolism/immunology; Child; Female; *Respiratory Syncytial Virus Infections/immunology/genetics; *Influenza, Human/immunology/genetics; Male; *Systemic Inflammatory Response Syndrome/immunology/genetics; Disease Models, Animal; SARS-CoV-2/immunology; Child, Preschool; Mice, Inbred C57BL; Granzymes/genetics
- Department(s)
- Infectious Diseases
- Publisher's Version
- https://doi.org/10.1038/s41467-025-65262-5
- Open Access at Publisher's Site
https://doi.org/10.1038/s41467-025-65262-5- Terms of Use/Rights Notice
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Creation Date: 2025-12-04 05:58:00
Last Modified: 2025-12-04 05:59:00