ACE2 and TMPRSS2 co-localization in proximal tubules from human kidneys obtained at autopsy from COVID-19 patients

ABSTRACT

Background: Studies at the single cell level have revealed that the localization of TMPRSS2 is in the distal nephron whereas ACE2 is in the proximal tubule. Since TMPRSS2 is a serine protease necessary for activation of the SARS-CoV-2 S spike protein after it binds to ACE2, this spatial separation would make it difficult to explain how SARS-CoV-2 can infect the kidney. The purpose of this study was to examine the localization of these proteins by immunofluorescence in the kidneys of patients who died from COVID-19. Methods: Human kidney slides from a Northwestern COVID-19 repository were used after IRB approval. Slides from paraffin-embedded blocks were probed with different antibodies (ACE2, TMPRSS2, ACE, NBC-1, Aquaporin 2) for immunofluorescence studies. Mouse kidneys were also examined as additional controls. Results: In mouse kidneys, TMPRSS2 was found in the brush border of proximal tubules and co-localized strongly with ACE2. Similarly, in human kidneys from patients who died from COVID-19, with or without AKI and from non-COVID-19 subjects, ACE2 and TMPRSS2 co-localized in the proximal tubule. TMPRSS2 and ACE2 also co-localized with ACE, a marker of the apical proximal tubule and to a lesser extent with NBC-1, a marker of the basolateral proximal tubule membrane. By contrast, TMPRSS2 and ACE2 did not co-localize with Aquaporin 2, a marker of principal cells in the collecting tubule. Conclusions: In both mouse and human kidneys, ACE2 and TMPRSS2 co-localize in the proximal tubule. In kidneys from patients with COVID-19 with or without AKI obtained at autopsy, both proteins co-localized in the proximal tubule but not in the collecting tubule. Contrary to what was suggested from single-cell mRNA analysis?, the co-localization of both proteins in the proximal tubule would make it possible for the SARS-CoV-2-ACE2 complex to be activated when coronavirus reaches the kidney.