Interleukin-3 protects against viral pneumonia in sepsis by enhancing plasmacytoid dendritic cell recruitment into the lungs and T cell priming

Benard A, Hansen F, Uhle F, Klösch B, Czubayko F, Mittelstädt A, Jacobsen A, David P, Podolska M, Anthuber A, Swierzy I, Schaack D, Mühl-Zürbes P, Steinkasserer A, Weyand M, Weigand MA, Brenner T, Krautz C, Grützmann R, Weber G (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Frontiers in Immunology Frontiers Research Foundation / Frontiers Media

Book Volume: 14

Article Number: 1140630

DOI: 10.3389/fimmu.2023.1140630

Abstract

Rationale: Sepsis, a global health burden, is often complicated by viral infections leading to increased long-term morbidity and mortality. Interleukin-3 (IL-3) has been identified as an important mediator amplifying acute inflammation in sepsis; however, its function in the host response to viral infections during sepsis remains elusive. Objectives: To investigate the role of IL-3 during viral pneumonia in sepsis. Methods: We included septic patients from two different cohorts and used in vitro and in vivo assays. The obtained data were substantiated using a second model (SARS-CoV-2 infections). Measurements and main results: Low plasma IL-3 levels were associated with increased herpes simplex virus (HSV) airway infections in septic patients, resulting in reduced overall survival. Likewise, Il-3-deficient septic mice were more susceptible to pulmonary HSV-1 infection and exhibited higher pulmonary inflammation than control mice. Mechanistically, IL-3 increases innate antiviral immunity by promoting the recruitment of circulating plasmacytoid dendritic cells (pDCs) into the airways and by enhancing pDC-mediated T cell activation upon viral stimulation. Interestingly, the ability of IL-3 to improve adaptive immunity was confirmed in patients with SARS-CoV-2 infections. Conclusion: Our study identifies IL-3 as a predictive disease marker for viral reactivation in sepsis and reveals that IL-3 improves antiviral immunity by enhancing the recruitment and the function of pDCs.

Authors with CRIS profile

Alan Benard Department of Surgery Frederik Hansen Medizinische Fakultät Franziska Czubayko Department of Surgery Anke Mittelstädt Department of Surgery Anne Jacobsen Department of Surgery Paul David Department of Surgery Malgorzata Podolska Department of Surgery Alexander Steinkasserer Professur für Experimentelle Dermatologie Michael Weyand Lehrstuhl für Herzchirurgie Christian Krautz Department of Surgery Robert Grützmann Department of Surgery Georg Weber Department of Surgery

Involved external institutions

Universitätsklinikum Heidelberg DE Germany (DE) Universitätsklinikum Essen DE Germany (DE)

How to cite

APA:

Benard, A., Hansen, F., Uhle, F., Klösch, B., Czubayko, F., Mittelstädt, A.,... Weber, G. (2023). Interleukin-3 protects against viral pneumonia in sepsis by enhancing plasmacytoid dendritic cell recruitment into the lungs and T cell priming. Frontiers in Immunology, 14. https://doi.org/10.3389/fimmu.2023.1140630

MLA:

Benard, Alan, et al. "Interleukin-3 protects against viral pneumonia in sepsis by enhancing plasmacytoid dendritic cell recruitment into the lungs and T cell priming." Frontiers in Immunology 14 (2023).

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