Pulmonary Myeloid Cells in Mild Cases of COVID-19 Upregulate the Intracellular Fc Receptor TRIM21 and Transcribe Proteasome-Associated Molecules

Much remains to be understood about COVID-19, but the protective role of antibodies (Igs) is widely accepted in SARS-CoV-2 infection. Igs' functions are mainly carried out by receptors that bind to their Fc portion (FcR), and less attention has been dedicated to the cytoplasmic members of this family. In this work, we used single-cell RNA sequencing (scRNA-seq) data to discern cell populations in bronchoalveolar lavage fluid obtained from healthy individuals and patients with mild or severe COVID-19. Then, we evaluated the transcription of neonatal FcR (FcRn, <i>FCGRT</i> gene) and tripartite motif-containing protein 21 (<i>TRIM21</i>) and its downstream signaling components. The TRIM21 pathway is vital for virus infections as it has a dual function, leading opsonized viruses to degradation by proteasomes and the activation of innate inflammatory anti-virus response. The transcriptional level of <i>FCGRT</i> showed no statistical differences in any cell population comparing the three groups of patients. On the other hand, <i>TRIM21</i> transcription was significantly higher in myeloid cells collected from patients with mild COVID-19. When comparing mild with severe cases, there was no statistical difference in <i>TRIM21</i> transcription in lung adaptive lymphoid cells and innate lymphoid cells (ILC). Yet, we analyzed the transcription of all downstream signaling molecules in myeloid and, as most cells expressed the receptor, in adaptive lymphoid cells. Moreover, ILCs from mild cases and all cell populations from severe cases were missing most downstream components of the pathway. We observed that members of the ubiquitin-proteasome system (UPS) and other components associated with TRIM21 proteasomal degradation were transcribed in mild cases. Despite the transcription of the danger sensors <i>DDX58</i> and <i>IFIH1</i>, the transcriptional level of inflammatory <i>IL1B</i> and <i>IL18</i> was generally very low, along with the <i>NLRP3</i> danger sensor, members of the NF-κB pathway, and <i>TNF</i>. Therefore, our data suggest that TRIM21 may contribute to SARS-CoV-2 protection by reducing the viral load, while the inflammatory branch of the pathway would be silenced, leading to no pathogenic cytokine production.