Antimicrobial lipids:Emerging effector molecules of innate host defense

The antimicrobial properties of host-derived derived lipids have become increasingly recognized and evidence is mounting that antimicrobial lipids （AMLs）, like antimicrobial peptides, are effector molecules of the innate immune system and are regulated by its conserved pathways. This review, with primary focus on the human body, provides some background on the biochemistry of lipids, summarizes their biological functions, expands on their antimicrobial properties and site-specifc composition, presents modes of synergism with antimicrobial peptides, and highlights the more recent reports on the regulation of AML production as well as bacterial resistance mechanisms. Based on extant data a concept of innate epithelial defense is proposed where epithelial cells, in response to microbial products and proinflammatory cytokines and through activation of conserved innate signaling pathways, increase their lipid uptake and up-regulate transcription of enzymes involved in antimicrobial lipid biosynthesis, and induce transcription of antimicrobial peptides as well as cytokines and chemokines. The subsequently secreted antimicrobial peptides and lipids then attack and eliminate the invader, assisted by or in synergism with other antimicrobial molecules delivered by other defense cells that have been recruited to the site of infection, in most of the cases. This review invites reconsideration of the interpretation of cholesteryl ester accumulation in macrophage lipid droplets in response to infection as a solely proinflammatory event, and proposes a direct antimicrobial role of lipid droplet- associated cholesteryl esters. Finally, for the interested, but new- to- the-feld investigator some starting points for the characterization of AMLs are provided. Before it is possible to utilize AMLs for anti-infectious therapeutic and prophylactic approaches, we need to better understand pathogen responses to these lipids and their role in the pathogenesis of chronic infectious disease.

The antimicrobial properties of host derived lipids have become increasingly recognized and evidence is mounting that antimicrobial lipids(AMLs),like antimicrobial peptides,are effector molecules of the innate immune system and are regulated by its conserved pathways.This review,with primary focus on the human body,provides some background on the biochemistry of lipids,summarizes their biological functions,expands on their antimicrobial properties and site-specific composition,presents modes of synergism with antimicrobial peptides,and highlights the more recent reports on the regulation of AML production as well as bacterial resistance mechanisms.Based on extant data a concept of innate epithelial defense is proposed where epithelial cells,in response to microbial products and proinflammatory cytokines and through activation of conserved innate signaling pathways,increase their lipid uptake and up-regulate transcription of enzymes involved in lipid biosynthesis,and induce transcription of antimicrobial peptides as well as cytokines and chemokines.The subsequently secreted antimicrobial peptides and lipids then attack and eliminate the invader,assisted by or in synergism with other antimicrobial molecules delivered by other defense cells that have been recruited to the site of infection,in most of the cases.This review invites reconsideration ofthe interpretation of cholesteryl ester accumulation in macrophage lipid droplets in response to infection as a solely proinflammatory event,and proposes a direct antimicrobial role of lipid droplet-associated cholesteryl esters.Finally,for the interested,but new-to-the-field investigator some starting points for the characterization of AMLs are provided.Before it is possible to utilize AMLs for anti-infectious therapeutic and prophylactic approaches,we need to better understand pathogen responses to these lipids and their role in the pathogenesis of chronic infectious disease.