eprintid: 31243 rev_number: 34 userid: 6685 dir: disk0/00/03/12/43 datestamp: 2017-06-29 23:08:34 lastmod: 2017-06-29 23:08:34 status_changed: 2017-06-29 23:08:34 type: thesis_degree metadata_visibility: show contact_email: dana.woell@gmail.com eprint_status: archive creators_name: Woell, Dana creators_email: dmw101@pitt.edu creators_id: dmw101 title: Impact of H5N1 influenza virus infection on natural killer cells and innate lymphoid cell populations in macaques ispublished: unpub divisions: sch_gsph_infectiousdiseasesmicrobiology full_text_status: public keywords: H5N1 abstract: Highly pathogenic avian influenza (HPAI) H5N1 viruses are a class of emerging zoonotic viruses that present a significant threat to global health. Seasonal influenza causes an estimated 3-5 million illnesses a year, presenting a significant public health burden. Surveillance and research into the clinical and immunological mechanisms of emerging avian influenza viruses like H5N1 with pandemic potential is important to safeguarding public health worldwide. H5N1 strains are endemic in wild and domestic birds worldwide, but very rarely infect humans. When spillover into humans does occur, however, H5N1 causes severe disease, acute respiratory distress, and has a high case fatality rate. The 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 are 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 H5N1 infected cynomolgous macaques. I found that NK cells showed a significant decrease in frequency in infected animals, perhaps indicating infection and subsequent loss relative to naïve animals. I was also able to identify two populations of CD45+ cells lacking lineage markers (CD3/CD20/CD163) in the macaque lung that are analogous to previously defined type 2 ILCs expressing CRTH2 but do not express CD127, and a population of type 3 ILCs that co-expressed CD127 and CD117. CRTH2+ cells accumulated non-significantly in the lungs of H5N1 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. date: 2017-06-29 date_type: published pages: 47 institution: University of Pittsburgh refereed: TRUE etdcommittee_type: committee_chair etdcommittee_type: committee_member etdcommittee_type: committee_member etdcommittee_name: Barratt-Boyes, Simon etdcommittee_name: Hartman, Amy etdcommittee_name: Wang, Jieru etdcommittee_email: smbb@pitt.edu etdcommittee_email: hartman2@pitt.edu etdcommittee_email: jiw95@pitt.edu etd_defense_date: 2017-04-18 etd_approval_date: 2017-06-29 etd_submission_date: 2017-04-03 etd_release_date: 2017-06-29 etd_access_restriction: immediate etd_patent_pending: FALSE thesis_type: thesis degree: MPH citation: Woell, Dana (2017) Impact of H5N1 influenza virus infection on natural killer cells and innate lymphoid cell populations in macaques. Master's Thesis, University of Pittsburgh. (Unpublished) document_url: http://d-scholarship-dev.library.pitt.edu/31243/1/Woell_Thesis_April_2017.pdf