CXCR3+ Alveolar macrophages help to clear viral load during SARS-CoV-2 infection 9049

Abstract Description Our goal was to understand the host immune response following the SARS-CoV-2 infection and finding an effective immune-therapeutic intervention. Mice infected with a mouse-adapted strain of SARS-CoV-2 (MA-10) showed increased CXCR3 signaling compared to sham-challenged mice, as observed by the increased expression of CXCR3 and its ligands CXCL9, CXCL10, and CXCL11 in lungs. Flow cytometry revealed that CXCR3+ T cells, Innate lymphoid cells, and macrophages were associated with the recovery following MA-10 infection. Interestingly, blocking CXCR3 signaling with monoclonal antibodies worsened disease outcomes measured by survival (P = 0.02), clinical scores (P = 0.006 on day 5 pi), and weight loss (P = 0.002 on day 5 pi). A plaque assay of lung lysates showed that aCXCR3 treated mice had impaired viral clearance (P = 0.02). Administering aCXCR3 showed a similar phenotype in Rag2-/- mice, suggesting that the CXCR3-mediated protection was conferred by innate immune cells. To investigate the role of alveolar macrophages, we stained for CD169, CD11c, and the SARS-CoV2 nucleocapsid. Immunostains confirmed that aCXCR3-treated mice had higher viral loads in the lungs. Although CD169+CD11c+ alveolar macrophages were comparable between the groups, the number of alveolar macrophages that phagocytosed viruses were significantly lower in aCXCR3 treated mice (P < 0.0001). We conclude that CXCR3 signaling in alveolar macrophages is indispensable to clear viral load during SARS-CoV2 infection. Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)