Membrane prohibitin forms a dynamic complex with p56 to regulate T cell receptor signaling.

Prohibitin is a highly conserved ubiquitously expressed protein involved in several key cellular functions. Targeting of this protein in the membrane by the virulence polysaccharide, Vi, of human typhoid-causing pathogen, Salmonella enterica serovar Typhi (S. Typhi), results in suppression of IL-2 secretion from T cells activated through the T-cell receptor (TCR).

ATP Release Drives Inflammation with Lysophosphatidylcholine.

Lysophosphatidylcholine (LPC), a dominant lipid component of oxidized low-density lipoprotein, plays a major role in inflammation associated with atherosclerosis and neurodegenerative disorders. It activates inflammatory responses from macrophages, neuronal cells, and endothelial cells. However, the exact mechanism by which LPC promotes inflammation remains incompletely understood.

Lysophosphatidylcholine Potentiates Antibacterial Activity of Polymyxin B.

Polymyxin B, used to treat infections caused by antibiotic-resistant Gram-negative bacteria, produces nephrotoxicity at its current dosage. We show that a combination of nonbactericidal concentration of this drug and lysophosphatidylcholine (LPC) potently inhibits growth of and at least two other Gram-negative bacteria This combination makes bacterial membrane porous and causes degradation of DnaK, the regulator of protein folding. Polymyxin B-LPC combination may be an effective and safer regimen against drug-resistant bacteria.

Serum-borne lipids amplify TLR-activated inflammatory responses.

TLRs recognize conserved pathogen associated molecular patterns and generate innate immune responses. Several circulating and cell membrane associated proteins have been shown to collaborate with TLRs in sensing microbial ligands and promoting inflammatory responses. Here, we show that serum and serum-borne lipids including lysophosphatidylcholine (LPC) amplify inflammatory responses from intestinal epithelial cells and mononuclear phagocytes primed with microbial TLR ligands.

Innate Activation of IFN-γ-iNOS Axis During Infection With Represses the Ability of T Cells to Produce IL-2.

Pathogenic serovars are a major cause of enteric illness in humans and animals, and produce clinical manifestations ranging from localized gastroenteritis to systemic disease. T cells are a critical component of immunity against this intracellular pathogen. The mechanisms by which modulates T-cell-mediated immune responses in order to establish systemic infection are not completely understood.