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Macrophages govern antiviral responses in human lung tissues protected from SARS-CoV-2 infection

ABSTRACT: The majority of SARS-CoV-2 infections among healthy individuals result in asymptomatic to mild disease. However, the immunological mechanisms defining effective lung tissue protection from SARS-CoV-2 infection remain elusive. Unlike mice solely engrafted with human fetal lung xenograft (fLX), mice co-engrafted with fLX and a myeloid-enhanced human immune system (HNFL mice) are resistant to SARS-CoV-2 infection, severe inflammation, and histopathology. Effective control of viral infection in HNFL mice associated with significant macrophage infiltration, and the induction of a potent macrophage-mediated interferon response. The strong upregulation of the USP18-ISG15 axis, a negative regulator of IFN responses, by macrophages was unique to HNFL mice and represented a prominent correlate of reduced inflammation and histopathology. Altogether, our work shed lights on unique cellular and molecular correlate of lung tissue protection during SARS-CoV-2 infection, and underscores macrophage IFN responses as prime targets for developing immunotherapies against coronavirus respiratory diseases.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE180908 | GEO | 2022/04/19

REPOSITORIES: GEO

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Macrophages govern antiviral responses in human lung tissues protected from SARS-CoV-2 infection

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