Discovery and characteristics of trained immunity
Freudenberg et al. 12 reported that in mice,
macrophages primarily stimulated by sepsis or high-dose
lipopolysaccharide (LPS) induce immune tolerance and exhibit a
suppressed immune response to avoid the development of a state of
excessive inflammation on secondary challenge. Quintin et al.13 also showed that whereas macrophages can be trained
by β-glucan (the main cell wall structural component of the yeastCandida albicans ), mice lacking functional T and B lymphocytes
are protected against reinfection of multiple pathogens such as C.
albicans and Staphylococcus aureus . Indeed, increasing number of
studies have indicated that bacterial, fungal, parasitic, and viral
infections can train monocytes/macrophages to promote the secretion of
inflammatory cytokines and enhance phagocytosis in response to secondary
stimulation, thereby confirming the universality of macrophage memory13-17. In addition to studies using animal models, a
study on childhood vaccination reported that the Bacillus
Calmette-Guérin (BCG) vaccination can enhance the defense against
infections other than those caused by mycobacteria in a
monocyte-dependent manner, thereby leading to an overall reduction in
child mortality 18. Furthermore, accumulating
epidemiological data indicates that live vaccines, such as the measles,
smallpox, and polio vaccines, provide non-specific protective effects
against a broad range of infections other than those caused by the
respective target viruses 19-22.
These studies have revealed two important characteristics of trained
immunity. Firstly, trained immunity is a non-specific or semi-specific
phenomenon, with its specificity being lower than that of adaptive
immunity; and as such, it can provide cross-protection against a wide
range of pathogens. Secondly, trained immunity primarily stimulated by
infections or vaccines induces a pro-inflammatory or anti-inflammatory
secondary immune response independent of classical T/B cell adaptive
immunity.