Fig. 3
From: An ongoing search for potential targets and therapies for lethal sepsis
HMGB1 orchestration of infection- and injury-elicited inflammatory responses. a A microbial infection triggers a systemic inflammatory response by stimulating active HMGB1 secretion or passive release. The disruption of epithelial barrier allows invasion of microbial pathogens, which liberate PAMPs and trigger the production of proinflammatory cytokines. Several proinflammatory cytokines can stimulate innate immune cells to actively secrete HMGB1 and trigger necroptosis that enables passive HMGB1 release. Collectively, extracellular HMGB1 facilitates leukocyte recruitment and activation, amplifying and sustaining rigorous inflammatory responses. b Injury triggers passive HMGB1 release. After injurious insult, HMGB1 is passively released by necrotic cells and functions as a DAMP signal that propagates rigorous inflammatory responses that are indistinguishable from infection-elicited inflammation