The alarmin IL-33 exacerbates pulmonary inflammation and immune dysfunction in SARS-CoV-2 infection

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

Research output: Contribution to journalArticlepeer-review


Dysregulated host immune responses contribute to disease severity and worsened prognosis in COVID-19 infection and 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 SARS-CoV-2-infected mice. Using IL-33−/− mice, we demonstrated that IL-33 deficiency resulted in significant decreases in bodyweight loss, tissue viral burdens, and lung pathology. These improved outcomes in IL-33−/− mice also correlated with a reduction in innate immune cell infiltrates, i.e., neutrophils, macrophages, natural killer cells, and activated T cells in inflamed lungs. Lung RNA-seq results revealed that IL-33 signaling enhances activation of inflammatory pathways, including interferon signaling, pathogen phagocytosis, macrophage activation, and cytokine/chemokine signals. Overall, these findings demonstrate that the alarmin IL-33 plays a pathogenic role in SARS-CoV-2 infection and provides new insights that will inform the development of effective therapeutic strategies for COVID-19.

Original languageEnglish (US)
Article number110117
Issue number6
StatePublished - Jun 21 2024


  • Immunology
  • Molecular network
  • Transcriptomics
  • Virology

ASJC Scopus subject areas

  • General


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