The role of T cells in sepsis of distinct infectious aetiologies

Abstract

Sepsis is a complex and life-threatening syndrome resulting from infection and characterized by dysregulated host immune responses. T cells play a central role in orchestrating immune defence against pathogens, yet their function undergoes profound alterations during sepsis. The impact of sepsis on T cell function varies depending on the causative pathogen. T cells exhibit an initial hyperactivation phase in bacterial sepsis, followed by a state of exhaustion, characterised by reduced cytokine production, impaired proliferation, and metabolic dysfunction. Such disorders are associated with disruptions in T cell receptor signalling, upregulation of immune checkpoint molecules such as PD-1 and CTLA4, and mitochondrial damage. T cell dysfunction is often linked to immunosuppression in viral sepsis, with an inhibition of antiviral responses and induction of immune tolerance. The distinct immune evasion strategies impair T cell-mediated pathogen clearance in viral sepsis, while altered T cell subsets are observed in fungal and parasitic sepsis. Such immune dysregulations exacerbate sepsis-induced immune suppression, increase susceptibility to secondary infections, and worsen clinical outcomes. Elucidating the pathogen-specific pathways that underlie T cell dysfunction in sepsis is crucial for the development of precise immunotherapies. These insights could inform the design of therapeutic strategies aimed at restoring T cell function and improving the prognosis of septic patients.

Keywords

immunosuppression / mitochondrial dysfunction / pathogen / sepsis / T cell

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