In:
The Journal of Immunology, The American Association of Immunologists, Vol. 204, No. 1_Supplement ( 2020-05-01), p. 231.29-231.29
Abstract:
Infection with Mycobacterium tuberculosis results in the formation of tuberculosis lung granulomas, which are complex structures with a network of multiple immune cells closely intertwined and function together. Within a given host, granulomas have unique trajectories and outcomes resulting in bacterial control or persistent bacterial replication and dissemination. The timing of establishment and immune composition of the granuloma in the lung plays a crucial role in the control of bacterial burden. Using high-throughput single-cell mRNA sequencing (SeqWell) on individual TB lung granulomas and computational algorithms, we are generating models to understand infection dynamics that incorporate timing of establishment, immune cell composition, its functional interactions; bacterial burden and trajectories of the granulomas to identify robust drivers of bacterial control. We evaluated original and new lung granulomas identified by PET CT scan from 15 cynomolgus macaques infected with M. tuberculosis (Erdman strain) for 4, 6 or 10 weeks. We identified over 30 functional clusters of cells spanning multiple immune and non-immune cells types including T cells, B cells, plasma cells, dendritic cells, mast cells, macrophages, neutrophils, pneumocytes, fibroblasts and endothelial cells. We observe differential cellular composition associated with temporal patterns (original vs. new) in granulomas that are associated with bacterial burden. By understanding these immune features associated with temporal patterns that limit bacterial replication, we hope to identify novel targets for host-directed immune therapies and prophylactics in M. tuberculosis infection and other granulomatous diseases.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.204.Supp.231.29
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2020
detail.hit.zdb_id:
1475085-5
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