Malvina Pizzuto

Abstract In Gram-negative bacterial sepsis, excessive caspase 4/11 activation in response to circulating bacterial lipid LPS (endotoxemia) can cause organ damage and mortality. Current inhibitors of caspase 4/11 also block caspase 1 activity and are therefore not appealing clinical candidates for treating Gram-negative sepsis.

Keywords ornithine lipids Toll-like receptor NLRP3 inflammasome bacteria lipopolysaccharide IL-1β ionizable lipid caspase TLR Research topic(s) CP: Immunology CP: Microbiology Introduction In the realm of bacterial attacks on a host immune system, much is known about phospholipids like lipopolysaccharides (LPS) stimulating an inflammatory reaction in the host.1,2 However, gram-negative bacteria reduce the production of phospholipids if they encounter a low-phosphate environment, such as...

Abstract Myeloid cells recognise Gram-negative bacterial lipopolysaccharides (LPS). LPS recognition triggers inflammatory reactions through Toll-like receptor 4 (TLR4) and primes the cells for inflammasome activation. In phosphate-depleted environments, bacteria cannot produce LPS. Instead, they increase their synthesis of ornithine lipid (OL), which is constitutively present in some pathogenic Gram-negative and -positive bacteria but absent in commensals.