Duncan NRI Faculty and Staff Publications
Language
English
Publication Date
9-15-2023
Journal
iScience
DOI
10.1016/j.isci.2023.107596
PMID
37664586
PMCID
PMC10470378
PubMedCentral® Posted Date
8-9-2023
PubMedCentral® Full Text Version
Post-print
Abstract
Recent studies suggest that infection reprograms hematopoietic stem and progenitor cells (HSPCs) to enhance innate immune responses upon secondary infectious challenge, a process called “trained immunity.” However, the specificity and cell types responsible for this response remain poorly defined. We established a model of trained immunity in mice in response to Mycobacterium avium infection. scRNA-seq analysis revealed that HSPCs activate interferon gamma-response genes heterogeneously upon primary challenge, while rare cell populations expand. Macrophages derived from trained HSPCs demonstrated enhanced bacterial killing and metabolism, and a single dose of recombinant interferon gamma exposure was sufficient to induce similar training. Mice transplanted with influenza-trained HSPCs displayed enhanced immunity against M. avium challenge and vice versa, demonstrating cross protection against antigenically distinct pathogens. Together, these results indicate that heterogeneous responses to infection by HSPCs can lead to long-term production of bone marrow derived macrophages with enhanced function and confer cross-protection against alternative pathogens.
Keywords
Cell biology, Immunology, Microbiology, Stem cells research, Transcriptomics
Published Open-Access
yes
Recommended Citation
Kain, Bailee N; Tran, Brandon T; Luna, Pamela N; et al., "Hematopoietic Stem and Progenitor Cells Confer Cross-Protective Trained Immunity in Mouse Models" (2023). Duncan NRI Faculty and Staff Publications. 171.
https://digitalcommons.library.tmc.edu/duncar_nri_pub/171
Graphical Abstract
Included in
Genetic Phenomena Commons, Medical Genetics Commons, Neurology Commons, Neurosciences Commons