Fig. 3

Infection-induced activation of key immune cells. In sepsis, bacterial infections trigger numerous pathways resulting in activation of key antigen-presenting cells (APCs) (i.e., monocytes/macrophages, dendritic cells). Activated APCs predominantly express pro-inflammatory cytokines and present antigens bound to major histocompatibility (MHC) class II complexes (such as HLA-DR). Antigen-bound HLA-DR triggers T-cell-receptor (TCR) and co-stimulatory molecule (e.g. CD 40-CD40L) binding. Adaptive immune responses are initiated resulting in clearance of infection. In, e.g., cases of overwhelming infection, deactivation of monocytes, as in sepsis-associated immunosuppression (SAI), may occur. SAI is characterized by a shift towards an anti-inflammatory phenotype with predominant expression of IL-10 and diminished HLA-DR expression, resulting in impaired clearance of infection and increased mortality. In IAI, the deactivated phenotype can be observed immediately after injury