Fig. 1

Schematic diagram of immune homeostasis imbalance in sepsis. The immune response is initiated when the host recognizes PAMPs and DAMPs. Inflammatory cells release pro-inflammatory cytokines and cause excessive inflammation in the early stage of inflammation. Under physiological conditions, the dynamic balance between pro-inflammatory and anti-inflammatory responses maintains immune homeostasis. However, after the onset of sepsis, the balance is disrupted. The upregulated expression of pro-inflammatory cytokines released by inflammatory cells and the activation of the complement and coagulation systems, result in excessive inflammation, which further leads to cytokine storms and MODS. Concurrently or subsequently, the increased release of anti-inflammatory cytokines and coinhibitory molecules, decreased expression of HLA-DR, death of immunocytes, and expansion of regulatory cells lead to immunosuppression, increasing the susceptibility to secondary infections, which is the main cause of poor prognosis in septic patients. TLR toll-like receptor, PAMP pathogen-associated molecular pattern, DAMP damage-associated molecular pattern, HLA-DR human leukocyte antigen-DR, MODS multiple organ dysfunction syndromes, Treg regulatory T cell, TIM-3 T-cell immunoglobulin domain and mucin domain-3, BTLA B and T lymphocyte antigens, PD-1 programmed cell death 1