Pattern recognition receptors, such as the C-type lectin receptor (CLR) family, play an important role in the generation of the innate immune response against a variety of pathogens. The CLR Macrophage galactose-type lectin (MGL), also known as CLEC10, is one member of this family which we and others found can bind SARS-CoV-2. MGL is known to increase in expression during SARS-CoV-2 infection and, in concert with other CLRs, is associated with elevated proinflammatory immune responses. Dexamethasone, a clinical treatment commonly used to mitigate the hyperinflammatory response in individuals with COVID-19, is also a positive stimulus for MGL expression. We therefore sought to investigate the role of MGL in disease pathogenesis using MGL-1 receptor deficient mice. Mice were intranasally infected with mouse adapted SARS-CoV-2 strain CMA3p20 and euthanized 3- or 7-days post infection. Following acute infection at 3 days, MGL-1 deficiency did not affect the viral burden in the lungs of mice. This was supported by multiplex cytokine and chemokine data which revealed similar acute inflammatory responses in the lung of infected WT and MGL-1 knockout (KO) mice. Interestingly, MGL-1 KO mice did display a significant increase in the lung viral burden when compared to WT mice 7 days post-infection. These results suggest a role for MGL-1 in resolution of SARS-CoV-2 at later stages of infection. Further investigations to determine differences in cellular recruitment and lung pathology in the absence of MGL-1 are warranted. In addition, assessment of a role for the MGL-2 orthologue expressed by murine myeloid cells may identify roles for MGL pathways in SARS-CoV-2 disease severity and pathogenesis.

Supported by UTMB Institute for Human Infection and Immunity COVID-19 Pilot Grant