FIGURE 4.

The Yin‐Yang balance of trained immunity. Trained immunity is a protective mechanism evolved to protect the host against infection and reinfection. However, a maladaptive effect of trained immunity can result in hyperinflammation, immune tolerance, or suppression that imbalance the immune systems. These compatible effects can be viewed as consistent with the Yin‐Yang theory of traditional Chinese philosophy, in which Yang represents the active, positive, and aggressive factors, whereas Yin represents the passive, negative, and inhibitory factors. The amicable (Yang) effects of trained immunity endow protection against infections such as COVID‐19, prevent sepsis, and can be utilized to optimize vaccination strategy. The detrimental (Yin) effects of trained immunity are associated with autoimmune and inflammatory disorders such as rheumatoid arthritis, atherosclerosis, neurodegenerative diseases and allergy, as well as contribution to allograft rejection in organ transplant surgery. The antitumor innate immune memory can hold both the Yang and Yin aspects: although BCG instillation induced trained immunity might be effective in treating bladder muscle cancer, the hyperactivated and chronic inflammation induced by trained immunity might also facilitate tumor growth. This figure was created with BioRender.com