"Problematic: Research on infectious diseases has high priority for the scientific and medical communities worldwide, to tackle the alarming spread of multidrug resistant bacteria, to fight and prevent virus outbreaks, and to improve patient management in severe infections including sepsis. Sepsis is recognised as one of the biggest challenges in modern healthcare. It kills as many as 30% of affected patients and leaves a lasting legacy even in those that survive. Although effective antimicrobials can improve the outcome of sepsis, diagnosis of the underlying infection is difficult and possible only in less than 60% of cases. A better understanding of the cellular and molecular signatures in acute disease may pave the way to earlier and more accurate diagnosis, targeted and personalised treatments and thus better outcomes. Research in the host laboratory at Cardiff University (Division of Infection and Immunity, School of Medicine) has shown that microbes interact at various levels with the immune system and leave disease-specific ""immune fingerprints"" that discriminate between different groups of organisms and inform the design of novel tests for infection diagnosis. Among the major breakthroughs in the understanding of host innate immune responses is the characterization of innate-like or unconventional T cells such as γδ T cells and mucosal-associated invariant T (MAIT) cells in acute disease. The organisms sensed by one or both of these unconventional T cell subsets include the causative agents of global health threats like tuberculosis and most hospital-acquired infections.
Objectives: The aim of the proposed project was to study the phenotype and function of innate immune cells during acute sepsis, with a particular focus on γδ T-cells and mucosal-associated invariant T (MAIT) cells. This translational research involved bed to bench-side approaches and addressed the potential of unconventional T cells to be exploited for novel diagnostics to predict the causative pathogen long before traditional culture results become available, and for novel therapies aimed at overcoming the detrimental immunosuppression frequently observed in sepsis and that is associated with poor clinical outcomes and elevated susceptibility to fatal second-hit infections.
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