Role of the neutrophil chemoattractant CXCL5 in the SARS-CoV-2 infection-induced lung inflammatory innate immune response determined using an in vivo hACE2 transfection mouse model

The emerging virus SARS-CoV-2 has caused a global pandemic, and understanding its pathogenesis and host antiviral immunity is critical for the development of vaccines and antivirals. Mice are frequently used to generate animal models of infectious diseases due to their convenience and ability to undergo genetic manipulation. However, normal adult mice are not susceptible to SARS-CoV-2. Here, we developed a viral receptor (human angiotensin-converting enzyme 2, hACE2) pulmonary transfection mouse model to rapidly establish SARS-CoV-2 infection in the mouse lung. Based on the model, the virus successfully infected the mouse lung after 2 days of transfection. Viral RNA/protein, innate immune cell infiltration, inflammatory cytokine expression, and pathological changes in the infected lung were observed after infection. Further studies indicated that neutrophils were the first and most abundant leukocytes that infiltrated the infected lung soon after viral infection. In addition, using infected CXCL5-knockout mice, the chemokine CXCL5 was found to be responsible for neutrophil recruitment. CXCL5 knockout decreased lung inflammation without diminishing viral clearance, suggesting a potential target for controlling pneumonia.