HMGB1 and infection: Post translational modifications such as acetylation, methylation, phosphorylation, and oxidation generally induce the active secretion of HMGB1, which is mediated through lysosomes [28], although, the exact mechanism of its active secretion is still unclear; however, it is revealed that upon infection, C5a engages with its receptor C5aR2 in macrophages that upregulates the expression of HMGB1 and is secreted through intracellular signaling [29].