Profiling superantigen-induced immunosuppression of unconventional T cells during sepsis (360G-Wellcome-217096_Z_19_Z)

£99,292

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