In:
Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-2-22)
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1664-3224
DOI:
10.3389/fimmu.2023.1140630
DOI:
10.3389/fimmu.2023.1140630.s001
DOI:
10.3389/fimmu.2023.1140630.s002
DOI:
10.3389/fimmu.2023.1140630.s003
DOI:
10.3389/fimmu.2023.1140630.s004
DOI:
10.3389/fimmu.2023.1140630.s005
DOI:
10.3389/fimmu.2023.1140630.s006
DOI:
10.3389/fimmu.2023.1140630.s007
DOI:
10.3389/fimmu.2023.1140630.s008
DOI:
10.3389/fimmu.2023.1140630.s009
DOI:
10.3389/fimmu.2023.1140630.s010
DOI:
10.3389/fimmu.2023.1140630.s011
DOI:
10.3389/fimmu.2023.1140630.s012
DOI:
10.3389/fimmu.2023.1140630.s013
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2023
detail.hit.zdb_id:
2606827-8
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