Project description:Current study of the mechanistic underpinnings of infectious disease is limited by an absence of human in vitro model systems which recapitulate the full spectrum of epithelial and immune responses induced by host-pathogen interactions. To address this gap, we describe a holistic, three-dimensional, air-liquid interface (ALI) lung organoid method from adult tissue comprising epithelial and stromal architecture along with a full complement of resident innate and adaptive immune cells. This novel system allows the study of the intrinsic tissue-resident immune function of the lung without requiring additional immune reconstitution from lung-extrinsic sources. Using SARS-CoV-2 infection of these 3D human lung ALI organoids, we demonstrate the ability of the endogenous immune system of the lung to mount a coordinated response including cytokine production, chemotaxis, adaptive CD4+ and CD8+ T-cell responses, and antibody production. Further, this immune response is dampened by inhibitors of viral replication and augmented in vaccinated individuals. Together, we describe the successful generation of human lung organoids that preserve the diversity of stromal and tissue-resident immune populations and SARS-CoV-2 infection thereof. This en bloc system demonstrates the sufficiency of lung to independently initiate anamnestic responses without a peripheral lymphoid component, as applicable to physiologic modeling of immune responses to SARS-CoV-2 and the broad study of pulmonary disease.

2023-08-08 | GSE216049 | GEO

Organoid modeling of lung-resident immune responses to SARS-CoV-2 infection

Project description:We sought to understand the effect of SARS-CoV-2 infection on transcriptomes of human lung organoids at various time points during infection.

2023-08-08 | GSE230398 | GEO

Reply to Soman et al, Alffenaar et al, Metcalfe et al, and Raoult.

Project description: Not available

| S-EPMC4696596 | biostudies-literature

Humanized mice for investigating SARS-CoV-2 lung infection and associated human immune responses.

Project description: Not available

| S-EPMC9538419 | biostudies-literature

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

Project description: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.

2022-04-19 | GSE180908 | GEO

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