Granulomas from Mycobacterium tuberculosis-infected macaques contain diverse populations of transcriptionally- and spatially-distinct macrophage subsets
Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B595
Abstract ID: 6055
Presenting Author:
Joshua T. Mattila , Assistant Professor at Univ. of Pittsburgh
Abstract:
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is characterized by granuloma formation. These immune cell aggregates can either restrict Mtb replication and aid in resolving the disease or, conversely, facilitate bacterial proliferation and worsen the pathology. Macrophages are key to these outcomes and understanding the diversity and function of macrophages within granulomas is vital for developing therapeutic strategies that promote protective immunity. In our study, we analyzed granulomas from macaques infected with mCherry-expressing Mtb, employing multi-modal scRNA-seq to delineate the macrophage subsets and identify Mtb-infected cells. Additionally, we utilized immunohistochemistry to map these subsets within the granulomas' spatial architecture. Our findings reveal a remarkable diversity of transcriptionally unique macrophages. Trajectory analysis suggests these cells originate either from tissue-resident alveolar macrophages or from recruited monocytes differentiating into alveolar or interstitial macrophages. Notably, these macrophage subsets occupy distinct positions within the granuloma, indicative of microenvironment-specific roles. Our results shed new light on macrophage biology in TB, revealing diverse functional states and spatial organization within granulomas. These insights enhance our understanding of immune cell dynamics in TB and pave the way for future research aimed at defining targeted immune strategies against this disease.
Granulomas from Mycobacterium tuberculosis-infected macaques contain diverse populations of transcriptionally- and spatially-distinct macrophage subsets
Category
Poster and Podium (Block Symposium)