Host immune response in sepsis: dysregulation, resistance, tolerance, and resilience

Apuntes

The net result is activation of pro-inflammatory pathways, in combination with immune dysfunction, including leukocyte anergy, lymphopenia, depletion of regulatory T cells and myeloid-derived suppressor cells, and reduced HLA-DR isotype expression by antigen-presenting cells. The altered functionality of both the innate and adaptive immune systems increases susceptibility to secondary infection from either external or intrinsic sources. Intrinsic sources include bowel microorganisms, such as Gram-negative bacteria and fungi16 and viral reactivation.17 Such infections impact recovery and can cause late deaths. The dysregulated immune response has been reframed as altered homoeostasis, with pathological disruption of immune-driven resistance, disease tolerance, resilience, and resolution (figure 3).18 Resistance refers to effector mechanisms that reduce the pathogen burden. Tolerance is an evolutionarily conserved defence strategy that limits disease severity without directly affecting pathogen burden.19 Resilience, with respect to the immune system, is the capacity to rapidly restore the pre-illness regulated Figure 1: Organ dysfunctions in sepsis Created in BioRender. Singer, M (20...