The Heat Shock Protein, gp96, initiates inflammatory responses by activation of inflammasome signaling platforms in macrophages

• Published in: The Journal of immunology (1950) Vol. 200; no. 1_Supplement; pp. 115 - 115.4
• Main Authors: Wang, Yifei, Binder, Robert J.
• Format: Journal Article
• Language: English
• Published: 01.05.2018
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.200.Supp.115.4

Abstract Several members of the heat shock protein family elicit immune responses which are, in part, a result of activation of antigen presenting cells. Activated antigen presenting cells respond to these immunogenic HSPs by up-regulating expression of co-stimulatory molecules and secretion of a panel of pro-inflammatory cytokines including IL-1b. We have tested here the requirement for activation of inflammasomes in the release of IL-1b by one immunogenic HSP, gp96. Our results show that macrophages activate NLRP3 inflammasomes in response to gp96, by K+ efflux. Using a gp96 secretion system we show that these events initiate inflammatory conditions in mice, in the absence of additional known inflammasome activators or infection. These results are important because the document a novel mechanism by which proteins of endogenous origin, the HSPs, can modulate a sterile inflammatory response following their release from cells are involved in host protection against infections by regulating IL-1b secretion via inflammsome activation.