Figure 2.

The effect of trained immunity on T cell responses will be key to determining the clinical relevance of trained immunity in mediating protection versus pathology. Trained immunity likely has an impact in many settings of infectious diseases and in immune mediated pathology. These clinically relevant effects may be mediated directly by the altered immune responses of myeloid cells but also indirectly by the effects of these myeloid cells on adaptive immune responses. (A) Trained immunity induced by β-glucan or BCG results in enhanced proinflammatory monocyte function which may promote the activation and differentiation of Th1 and Th17 cells whilst concomitantly downregulating Treg cell responses. This may be beneficial in promoting protection against infection but may be pathogenic in settings of immune mediated pathology such as in autoimmunity or atherosclerosis. (B) Fasciola hepatica total extract (FHTE) induces trained immunity which results in enhanced anti-inflammatory responses. This may be beneficial in attenuating autoimmune diseases but may promote cancer or allergy. (C) LPS induced trained immunity followed by restimulation with LPS results in tolerance. This induces Treg cells and is thought be pathological during sepsis.