Cord blood-derived dendritic cells as a model for investigating IAV-Induced innate and adaptive Immunity 4423

Description Influenza virus A (IAV) is a respiratory pathogen transmitted via aerosol and circulating annually in humans. Despite numerous animal models and clinical studies on influenza infection and vaccination, our understanding of IAV’s interaction with human immune cells remains limited. Here, we developed a human cord blood hematopoietic stem cell (HSC) -derived dendritic cell (DC) model to study innate and adaptive immune responses induced by different IAV strains in different DC subsets ex vivo. Research in human monocyte-derived DCs (moDCs) shows that the nonstructural 1 (NS1) protein of IAV is a key antagonist of the innate immune response in DCs, blocking their activation. We used recombinant human IAV virus lacking NS1 (A/Texas/36/99) previously reported by us to induce type I interferon (IFN) mediated innate immune response in monocyte-derived DCs (moDCs) as compared to A/Texas/36/91 WT (Haye et al. 2009). HSC- derived DCs were infected with these viruses, and their immune profiles were assessed for the upregulation of activation markers over time. Our results show that, similar to moDCs, HSC-derived DCs exhibited an activated innate immune profile in response to NS1-mutant A/Texas/36/99 infection but did not produce Type I IFN responses after exposure to WT strain. Our results highlight the suitability of this model for studying human host responses to IAV, providing a valuable tool for advancing our understanding of immune mechanisms and improving vaccine strategies.