Immediate myeloid depot for SARS-CoV-2 in the human lung

Area of Science:

• Immunology
• Virology
• Pathogenesis

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis is not fully understood, especially viral expansion and immune cell interactions in the distal lung.
• Epithelial cells expressing Angiotensin-converting enzyme 2 (ACE2) are infrequent in the distal lung, complicating early infection models.

Purpose of the Study:

• To investigate early host-viral pathogenesis of SARS-CoV-2 in human lungs.
• To determine the tropism and replication dynamics of SARS-CoV-2 in lung myeloid populations.

Main Methods:

• Utilized human lung tissue to study early host-viral interactions.
• Investigated SARS-CoV-2 entry and infection in alveolar macrophages (AMs).
• Compared SARS-CoV-2 infection dynamics with Influenza A virus in AMs.

Main Results:

• SARS-CoV-2 demonstrated rapid and specific tropism for myeloid populations, particularly alveolar macrophages (AMs).
• Human AMs expressed ACE2, facilitating SARS-CoV-2 entry and productive infection, leading to amplified viral titers.
• SARS-CoV-2 infection of AMs resulted in muted interferon responses, masking viral dissemination from antiviral immunity.

Conclusions:

• Alveolar macrophages (AMs) serve as a key cellular reservoir for SARS-CoV-2 in early lung infection.
• The muted immune response in infected AMs facilitates viral expansion and may predispose to subsequent immune pathologies.
• Understanding myeloid cell tropism is crucial for developing effective SARS-CoV-2 therapeutics.