Back to Search
Start Over
Beneficial effects of citrulline enteral administration on sepsis-induced T cell mitochondrial dysfunction
- Source :
- Proceedings of the National Academy of Sciences of the United States of America, Proceedings of the National Academy of Sciences of the United States of America, 2022, 119 (8), pp.e2115139119. ⟨10.1073/pnas.2115139119⟩, Proceedings of the National Academy of Sciences of the United States of America, 119(8):e2115139119. National Academy of Sciences
- Publication Year :
- 2022
-
Abstract
- International audience; Severe sepsis induces a sustained immune dysfunction associated with poor clinical behavior. In particular, lymphopenia along with increased lymphocyte apoptosis and decreased lymphocyte proliferation, enhanced circulating regulatory T cells (Treg), and the emergence of myeloid-derived suppressor cells (MDSCs) have all been associated with persistent organ dysfunction, secondary infections, and late mortality. The mechanisms involved in MDSC-mediated T cell dysfunction during sepsis share some features with those described in malignancies such as arginine deprivation. We hypothesized that increasing arginine availability would restore T cell function and decrease sepsis-induced immunosuppression. Using a mouse model of sepsis based on cecal ligation and puncture and secondary pneumonia triggered by methicillin-resistant Staphylococcus aureus inoculation, we demonstrated that citrulline administration was more efficient than arginine in increasing arginine plasma levels and restoring T cell mitochondrial function and proliferation while reducing sepsis-induced Treg and MDSC expansion. Because there is no specific therapeutic strategy to restore immune function after sepsis, we believe that our study provides evidence for developing citrulline-based clinical studies in sepsis.
- Subjects :
- Immunosuppression Therapy
Multidisciplinary
Myeloid-Derived Suppressor Cells
T-Lymphocytes
[SDV]Life Sciences [q-bio]
Biological Availability
T cell
[SDV.CAN]Life Sciences [q-bio]/Cancer
Arginine
Lymphocyte Activation
T-Lymphocytes, Regulatory
Mitochondria
Mice, Inbred C57BL
[SDV] Life Sciences [q-bio]
Disease Models, Animal
Mice
[SDV.CAN] Life Sciences [q-bio]/Cancer
Sepsis
Immune Tolerance
Animals
Cytokines
Citrulline
Female
Subjects
Details
- Language :
- English
- ISSN :
- 00278424 and 10916490
- Volume :
- 119
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Accession number :
- edsair.doi.dedup.....ccecb596ac79fa1f8dccbf20e14ccb3e