02760nas a2200493   4500000000100000008004100001260001300042653002500055653002000080653002000100653001100120653002100131653002500152653001700177653001200194653002100206653002200227653001600249653001400265653002500279653002400304653002500328653001800353100001100371700001400382700001400396700001500410700001200425700001500437700001600452700001200468700001300480700001400493700001600507700001000523700001600533700001500549700001400564245009100578300001200669490000800681520156300689022001402252       2008                            d  c2008 Aug10aCell Differentiation10aCells, Cultured10aDendritic Cells10aHumans10aImmunity, Innate10aImmunohistochemistry10aIsoprostanes10aleprosy10aLipid Metabolism10aLipoproteins, HDL10aMacrophages10aMonocytes10aMycobacterium leprae10aOxidation-Reduction10aPhosphatidylcholines10aPhospholipids1 aCruz D1 aWatson AD1 aMiller CS1 aMontoya DJ1 aOchoa M1 aSieling PA1 aGutierrez M1 aNavab M1 aReddy ST1 aWitztum J1 aFogelman AM1 aRea T1 aEisenberg D1 aBerliner J1 aModlin RL00aHost-derived oxidized phospholipids and HDL regulate innate immunity in human leprosy.  a2917-280 v1183 a<p>Intracellular pathogens survive by evading the host immune system and accessing host metabolic pathways to obtain nutrients for their growth. Mycobacterium leprae, the causative agent of leprosy, is thought to be the mycobacterium most dependent on host metabolic pathways, including host-derived lipids. Although fatty acids and phospholipids accumulate in the lesions of individuals with the lepromatous (also known as disseminated) form of human leprosy (L-lep), the origin and significance of these lipids remains unclear. Here we show that in human L-lep lesions, there was preferential expression of host lipid metabolism genes, including a group of phospholipases, and that these genes were virtually absent from the mycobacterial genome. Host-derived oxidized phospholipids were detected in macrophages within L-lep lesions, and 1 specific oxidized phospholipid, 1-palmitoyl-2-(5,6-epoxyisoprostane E2)-sn-glycero-3-phosphorylcholine (PEIPC), accumulated in macrophages infected with live mycobacteria. Mycobacterial infection and host-derived oxidized phospholipids both inhibited innate immune responses, and this inhibition was reversed by the addition of normal HDL, a scavenger of oxidized phospholipids, but not by HDL from patients with L-lep. The accumulation of host-derived oxidized phospholipids in L-lep lesions is strikingly similar to observations in atherosclerosis, which suggests that the link between host lipid metabolism and innate immunity contributes to the pathogenesis of both microbial infection and metabolic disease.</p>  a0021-9738