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Exploring macrophage phenotypic and functional diversity in granulomas from Mycobacterium tuberculosis-infected macaques

Nelson, Molly (2024) Exploring macrophage phenotypic and functional diversity in granulomas from Mycobacterium tuberculosis-infected macaques. Master's Thesis, University of Pittsburgh. (Unpublished)

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Tuberculosis (TB) is an infectious disease that can be found all around the globe. The disease is caused by the bacteria Mycobacterium tuberculosis. In response to infection, the immune response surrounds the bacteria to stop the growth and dissemination known as a granuloma. A granuloma consists of different types of immune cells with a large fraction of the cells being macrophages. Each granuloma that develops is unique in its cellular makeup. Little is known about the diversity of macrophages that exist inside the granuloma but learning more about these cells in the granuloma can lead to targeted therapeutics, improved vaccine candidates, and an overall improvement to the understanding of TB. Using non-human primates infected with M. tuberculosis, I explored the spatial location of different macrophages populations after they were revealed by a cyclic immunohistochemistry staining process on formalin-fixed paraffin-embedded tissues and mapped their locations with software programs. Data rich images were segmented into the cell populations and spatially represented for an easier way to visualize the data. From the mapping it was seen that macrophage populations clustered into four subsets alveolar macrophage like cells, lymphocyte cuff macrophages, epithelioid macrophages, and mixed phenotype macrophages. Each subset of macrophage populations had a different spatial location in the microenvironment. Data was also analyzed through a PCA analysis to identify clusters of cells that are positive for pSTAT1 and pSMAD3. The overall results demonstrate the complexity of macrophage populations and where they localize within tuberculous granuloma microenvironment.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Nelson, Mollymon23@pitt.edumon23
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairMattila, Joshua T.jmattila@pitt.edujmattila
Committee MemberDa Silva Castanha, Priscilapmd35@pitt.edupmd35
Committee MemberBuchanich, Jeaninejeanine@pitt.edujeanine
Date: 17 May 2024
Date Type: Publication
Defense Date: 12 April 2024
Approval Date: 17 May 2024
Submission Date: 23 April 2024
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 73
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Infectious Diseases and Microbiology
Degree: MPH - Master of Public Health
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Tuberculosis, macrophages, granulomas, spatial data, QuPath, CytoMAP, mapping
Date Deposited: 17 May 2024 18:00
Last Modified: 17 May 2024 18:00


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