MAP Kinase Signaling at the Crossroads of Inflammasome Activation.

Inflammasomes are crucial mediators of both antimicrobial host defense and inflammatory pathology, requiring stringent regulation at multiple levels. This review explores the pivotal role of mitogen-activated protein kinase (MAPK) signaling in modulating inflammasome activation through various regulatory mechanisms. We detail recent advances in understanding MAPK-mediated regulation of NLRP3 inflammasome priming, licensing and activation, with emphasis on MAPK-induced activator protein-1 (AP-1) signaling in NLRP3 priming, ERK1 and JNK in NLRP3 licensing, and TAK1 in connecting death receptor signaling to NLRP3 inflammasome activation.

Infection history imprints prolonged changes to the epigenome, transcriptome and function of Kupffer cells.

Background & Aims: Liver macrophages fulfill various homeostatic functions and represent an essential line of defense against pathogenic insults. However, it remains unclear whether a history of infectious disease in the liver leads to long-term alterations to the liver macrophage compartment.

Methods: We utilized a curable model of parasitic infection invoked by the protozoan parasite Trypanosoma brucei brucei to investigate whether infection history can durably reshape hepatic macrophage identity and function.

Oxylipins and metabolites from pyroptotic cells act as promoters of tissue repair.

Pyroptosis is a lytic cell death mode that helps limit the spread of infections and is also linked to pathology in sterile inflammatory diseases and autoimmune diseases. During pyroptosis, inflammasome activation and the engagement of caspase-1 lead to cell death, along with the maturation and secretion of the inflammatory cytokine interleukin-1β (IL-1β). The dominant effect of IL-1β in promoting tissue inflammation has clouded the potential influence of other factors released from pyroptotic cells.