Conference Room 2140 Parran Hall

"Impact of H5N1 Influenza Virus Infection

of Macaques on Natural Killer Cells

and Innate Lymphoid Cell Populations"

Abstract:  Highly pathogenic avian influenza (HPAI) H5N1 viruses are an emerging zoonotic disease that presents a significant threat to global health.  H5N1 strains are endemic in wild and domestic birds worldwide, but very rarely infects humans.  When spillover into humans does occur, however, H5N1 causes severe disease, acute respiratory distress, and has a high case fatality rate.  This high pathogenic potential of this virus makes a compelling argument for understanding the underlying pathological and immunological mechanisms of the disease.  Our lab has demonstrated in a nonhuman primate model that aerosolized infection with H5N1 influenza virus leads to disease progression similar to that seen in human cases.  This study aims to characterize some of the innate immune cells that contribute to the response to severe H5N1 infection in this macaque model.  Natural killer (NK) cells are a critical cytotoxic innate responder to viral infection, and innate lymphoid cells (ILCs) are a recently discovered subset of the innate immune system that is thought to have a critical impact on early response to viral infection in the lung.  These cells were characterized and quantified in lung tissue of both naïve and infected cynomolgous macaques.  We found that NK cells showed a significant decrease in infected animals.  We were also able to identify two populations of lineage- CD45+ cells in the macaque lung that are analogous to previously defined type 2 ILCs expressing CRTH2 but do not CD127, and a population of type 3 ILCs that co-expressed CD127 and CD117.  CRTH2+ cells accumulated non-significantly in the lungs of infected animals in response to influenza virus, suggesting that they are stimulated and recruited by infection, and likely have a protective immune response.  Further characterization of ILC and NK cell subsets in the lung and their functional response to severe acute respiratory infection such as H5N1 provides a promising avenue for understanding the early innate response to influenza infection.