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Impact of H5N1 influenza virus infection on natural killer cells and innate lymphoid cell populations in macaques

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 (Unpublished)

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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.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Woell, Danadmw101@pitt.edudmw101
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairBarratt-Boyes, Simonsmbb@pitt.edu
Committee MemberHartman, Amyhartman2@pitt.edu
Committee MemberWang, Jierujiw95@pitt.edu
Date: 29 June 2017
Date Type: Publication
Defense Date: 18 April 2017
Approval Date: 29 June 2017
Submission Date: 3 April 2017
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 47
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Degree: MPH - Master of Public Health
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: H5N1
Date Deposited: 29 Jun 2017 23:08
Last Modified: 29 Jun 2017 23:08
URI: http://d-scholarship.pitt.edu/id/eprint/31243

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