Profiling superantigen-induced immunosuppression of unconventional T cells during sepsis (360G-Wellcome-217096_Z_19_Z)
Sepsis is a life-threatening illness that is triggered by an exaggerated immune response to severe infection. Despite improving survival rates, patients are often left immunosuppressed. This defining feature is considered to be the main driving force behind morbidity and mortality in sepsis. Staphylococcus aureus is a leading cause of sepsis and, like other bacteria, secretes potent exotoxins (superantigens) which suppress, or even deplete, circulating T cell populations, including antimicrobial T cells (MAIT cells, gammadelta T cells). These "unconventional" T cells are known to be depleted in the blood of sepsis patients yet our knowledge on a link between the action of superantigens and unconventional T cell depletion in sepsis is incomplete. This proposal will use advanced polychromatic flow cytometry and RNA sequencing to profile the immunosuppressive actions of a panel of bacterial superantigens (cellular exhaustion, excessive cytokine production) on antimicrobial human T cells. Using cohort of patients with acute bacterial sepsis, correlations between patterns of superantigen-induced immunosuppression and depleted MAIT and gammadelta T cells in sepsis will be examined. This approach will aim to determine whether superantigens promote the depletion of certain MAIT and gammadelta T cell clonotypes during sepsis, providing novel insight into the pathogenic mechanisms driving sepsis-mediated immunosuppression.
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Grant Details
Amount Awarded | 99292 |
Applicant Surname | McLaren |
Approval Committee | Science Seeds Advisory Panel |
Award Date | 2019-04-11T00:00:00+00:00 |
Financial Year | 2018/19 |
Grant Programme: Title | Seed Award in Science |
Internal ID | 217096/Z/19/Z |
Lead Applicant | Dr James McLaren |
Partnership Value | 99292 |
Planned Dates: End Date | 2022-09-30T00:00:00+00:00 |
Planned Dates: Start Date | 2019-10-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Wales |