Destabilisation of T cell-dependent humoral immunity in sepsis.
Kate Megan Megan DaviesJames E McLarenPublished in: Clinical science (London, England : 1979) (2024)
Sepsis is a heterogeneous condition defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For some, sepsis presents as a predominantly suppressive disorder, whilst others experience a pro-inflammatory condition which can culminate in a 'cytokine storm'. Frequently, patients experience signs of concurrent hyper-inflammation and immunosuppression, underpinning the difficulty in directing effective treatment. Although intensive care unit mortality rates have improved in recent years, one-third of discharged patients die within the following year. Half of post-sepsis deaths are due to exacerbation of pre-existing conditions, whilst half are due to complications arising from a deteriorated immune system. It has been suggested that the intense and dysregulated response to infection may induce irreversible metabolic reprogramming in immune cells. As a critical arm of immune protection in vertebrates, alterations to the adaptive immune system can have devastating repercussions. Indeed, a marked depletion of lymphocytes is observed in sepsis, correlating with increased rates of mortality. Such sepsis-induced lymphopenia has profound consequences on how T cells respond to infection but equally on the humoral immune response that is both elicited by B cells and supported by distinct CD4+ T follicular helper (TFH) cell subsets. The immunosuppressive state is further exacerbated by functional impairments to the remaining lymphocyte population, including the presence of cells expressing dysfunctional or exhausted phenotypes. This review will specifically focus on how sepsis destabilises the adaptive immune system, with a closer examination on how B cells and CD4+ TFH cells are affected by sepsis and the corresponding impact on humoral immunity.
Keyphrases
- intensive care unit
- septic shock
- immune response
- acute kidney injury
- end stage renal disease
- chronic kidney disease
- induced apoptosis
- newly diagnosed
- ejection fraction
- cardiovascular events
- peripheral blood
- coronary artery disease
- chronic obstructive pulmonary disease
- dendritic cells
- squamous cell carcinoma
- prognostic factors
- cell cycle arrest
- inflammatory response
- risk factors
- mesenchymal stem cells
- cell proliferation
- signaling pathway
- patient reported outcomes
- smoking cessation
- stem cells
- cell therapy
- rectal cancer