Impact of toxoplasma gondii on treg homeostasis
Ended Project Grant Awarded Last action
- Award ID
- F31AI179240
- Recipient
-
The Trustees Of The University Of Pennsylvania UEI GM1XX56LEP58
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $152,554
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date
- Place of performance
- Philadelphia, PA 19104, USA
Award details come from USAspending.gov.
Description
- Abstract
- Acute infection of mice with toxoplasma gondii results in a collapse of the regulatory T cell (TREG) population. While the infection-induced collapse of TREG cells has been defined, the RE-building of the compartment and the long-term impact of the crash have not been studied. Tregs were originally believed to be a monolithic population of suppressor cells, but there is recognition of distinct subsets termed central and effector tregs. At homeostasis, central tregs (CTREGS) are a relatively quiescent subset whereas effector tregs (ETREGS) exhibit hallmarks of recent TCR engagement and potent suppressive activity. The studies presented here reveal that infection results in a skewing of the composition of the TREG compartment after the collapse. My data shows as infection resolves, there is restoration of IL-2 production and thymic output and the TREG compartment returns to near normal levels, yet there remains a marked increase in the ratio of ctreg:etreg cells. The use of lineage tracing shows that the post-crash TREG compartment is dominated by TREG cells that were present during collapse but a population of newly-generated tregs emerge from the thymus these observations raise fundamental questions about the rebuilding process: (1) what cytokines contribute to RE-population? (2) does ongoing inflammation associated with chronic infection affect TREG output and phenotype? And (3) does the TREG collapse lead to permanent alterations to the population structure or function of the TREG compartment? To get at these questions, I will utilize high-parameter flow cytometry, multi-omic sequencing and an in vivo TREG tracing model to investigate the TREG compartment throughout infection with T.gondii. I will interrogate the impact of IL-2 and IL-7 on TREG RE-population and determine how infection shapes the RE-built TREG compartment. These studies will enhance our understanding of TREG biology during infection and identify possible approaches for manipulating TREG subsets therapeutically.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | -$20,128 | |
| Amendment | $37,367 | |
| Amendment | $37,367 | |
| Amendment | $48,974 | |
| Amendment | $0 | |
| Original award | $48,974 |
Quick answers
Who received award F31AI179240?
F31AI179240 was awarded to The Trustees Of The University Of Pennsylvania by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on January 24, 2025.
How much is award F31AI179240 worth?
$152,554 has been obligated on F31AI179240.
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