Figure 2.

Immune responses of endogenous/exogenous riboflavin and exogenous riboflavin against infection. a. The formation of pyrimidine adducts. 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU) and 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU) are formed by (5) combining with glyoxal or methylglyoxal in bacteria. RF: riboflavin. b. Interaction between riboflavin and MAIT cells. MR1 recognizes and presents the signals of the riboflavin synthesis pathway to MAIT cells triggering different types of immune responses in bacteria and fungi. 1) MIAT cells produce granzyme B and perforin to kill the target cell directly. 2) MAIT cells release cytokines, including IFN-γ, GM-CSF, IL-17, and TNF. 3) MAIT cells facilitate other immune cells to protect the host from infection. However, fungi are recognized in an MR1-dependent manner and, therefore, MAIT cells response to fungi are not exactly same as to bacteria. Viruses cannot biosynthesize riboflavin, and depend on cytokines to activate MAIT cells. In most virus infections, MAIT cells levels were reduced and their functions were impaired, such as antimicrobial activity. In addition, activated MAIT cells can limit HCV replication, and the mechanism should be further explored. c. The immune responses of exogenous riboflavin against infection. Exogenous riboflavin affects infectious disease by regulating the function of immune cells and the release of cytokines/inflammatory factors. HMGB1: high mobility group box 1 protein, Mø: macrophage, PMN: polymorphonuclear cell. INF-γ: interferon-γ, TNF-α: tumor necrosis factor-α, MCP-1: monocyte chemoattractant protein-1, IL: interleukin, Hsp: heat shock protein