Single-cell analysis of pig lung leukocytes and their response to influenza infection and oseltamivir therapy

Abstract Despite pigs being an important species in influenza A virus (IAV) epidemiology and a reliable preclinical model for human IAV infections, many aspects of the porcine pulmonary immune system remain poorly understood. Here, we characterized the single-cell landscape of lung leukocytes of healthy pigs and then compared them to pigs infected with 2009 pandemic H1N1 IAV with or without oseltamivir antiviral therapy. Our data show conserved features as well as species-specific differences in cell types and cell states compared with human and mouse lung lymphocytes. IAV infection induced a robust antiviral transcriptional response in multiple lymphoid and myeloid cell types, as well as distinct patterns of cell-cell crosstalk. Oseltamivir treatment substantially reduced these responses. Together, our findings describe key events in the pulmonary anti-IAV response of pigs that open new avenues to develop IAV vaccines and therapies. They should also enable the better use of pigs as a model for human IAV infection and immunity.