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The Alarmin IL-33 Exacerbates Pulmonary Inflammation and Immune Dysfunction in SARS-CoV-2 Infection

SSRN, ISSN: 1556-5068
2024
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  • Usage
    296
    • Abstract Views
      281
    • Downloads
      15

Article Description

Dysregulated host immune responses crucially contribute to the severity and poor recovery of COVID-19; yet the underlying mechanisms are not fully understood. In this study, we observed that IL-33, a damage-associated molecular pattern molecule, is significantly increased in COVID-19 patients and in the SARS-CoV-2-infected mice. Using IL-33-/- mice, we demonstrated that IL-33 deficiency is associated with significantly reduced bodyweight loss, tissue viral burdens, and lung pathology. This improved infection outcome in IL-33-/- mice correlated with reduced infiltrates of innate immune cells, i.e., neutrophils, macrophages, and natural killer cells, and activated T cells in inflamed lungs. Lung RNA-seq data revealed that IL-33 signaling enhances activation of inflammatory pathways, including interferon signaling, pathogen phagocytosis, macrophage activation and cytokine/chemokine. These findings unveil a pathogenic role of the alarmin IL-33 in SARS-CoV-2 infection, providing new insights that support the development of effective therapeutic strategies for COVID-19.

Bibliographic Details

Hui Wang; Paul J. Boor; Casey Gonzales; Ping Ren; Lynn Soong; Jiaren Sun; Yashoda M. Hosakote; Yuejin Liang; Haitao Hu; Keer Sun; Jun Yang; Corri B. Levine; Susan McLellan; Nicole Cloutier; Yuanyi Zhang; Xiaoying Yu; Xuping Xie; Pei Yong Shi

Elsevier BV

Multidisciplinary; IL-33; COVID-19; SARS-CoV-2; innate immunity; inflammation; lung

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