Editorial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Immunol. Jul 27, 2015; 5(2): 51-61
Published online Jul 27, 2015. doi: 10.5411/wji.v5.i2.51
Antimicrobial lipids: Emerging effector molecules of innate host defense
Edith Porter, Daniel C Ma, Sandy Alvarez, Kym F Faull
Edith Porter, Daniel C Ma, Sandy Alvarez, Department of Biological Sciences, California State University Los Angeles, Los Angeles, CA 90032, United States
Edith Porter, Department of Medicine, Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, United States
Daniel C Ma, University of Iowa Carver College of Medicine, Iowa City, IA 52242, United States
Kym F Faull, Pasarow Mass Spectrometry Laboratory, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA 90095, United States
Author contributions: Porter E, Ma DC, Alvarez S and Faull KF contributed to conception and design of the study, literature search and analysis and interpretation of data; Porter E drafted the article; Ma DC, Alvarez S and Faull KF made critical revisions related to important intellectual content of the manuscript; all authors gave final approval of the version of the article to be published.
Supported by The National Institutes of Health, Nos. 1R21AI55675, 1P20MD001824, 1SC1GM096916 and 1S10RR023718-01A2; and by the Cystic Fibrosis Foundation, Pilot Research, No. PORTER12I0.
Conflict-of-interest statement: The authors declare no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Edith Porter, MD, Professor of Microbiology and Immunology, Department of Biological Sciences, California State University Los Angeles, 5151 State University Drive, Los Angeles, CA 90032, United States. eporter@calstatela.edu
Telephone: +1-323-3436353 Fax: +1-323-3436451
Received: May 20, 2015
Peer-review started: May 21, 2015
First decision: June 18, 2015
Revised: June 24, 2015
Accepted: July 16, 2015
Article in press: July 17, 2015
Published online: July 27, 2015
Processing time: 75 Days and 18.7 Hours
Abstract

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 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-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.

Keywords: Atopic dermatitis; Cholesterol; Infectious disease; Cystic fibrosis; Mucosa

Core tip: The antimicrobial properties of host derived lipids have become increasingly recognized. This review develops the concept of antimicrobial lipids (AMLs) as effectors of the innate immune response that work together with antimicrobial peptides to prevent infection, and highlights more recent reports on the regulation of AML production as well as bacterial resistance mechanisms. Furthermore, 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.