Innate immune detection of lipid oxidation as a threat assessment strategy

Abstract

Oxidized phospholipids that result from tissue injury operate as immunomodulatory signals that, depending on the context, lead to proinflammatory or anti-inflammatory responses. In this Perspective, we posit that cells of the innate immune system use the presence of oxidized lipids as a generic indicator of threat to the host. Similarly to how pathogen-associated molecular patterns represent general indicators of microbial encounters, oxidized lipids may be the most common molecular feature of an injured tissue. Therefore, microbial detection in the absence of oxidized lipids may indicate encounters with avirulent microorganisms. By contrast, microbial detection and detection of oxidized lipids would indicate encounters with replicating microorganisms, thereby inducing a heightened inflammatory and defensive response. Here we review recent studies supporting this idea. We focus on the biology of oxidized phosphocholines, which have emerged as context-dependent regulators of immunity. We highlight emerging functions of oxidized phosphocholines in dendritic cells and macrophages that drive unique inflammasome and migratory activities and hypermetabolic states. We describe how these lipids hyperactivate dendritic cells to stimulate antitumour CD8 + T cell immunity and discuss the potential implications of the newly described activities of oxidized phosphocholines in host defence.

l-Arginine and COVID-19: An Update

“…A direct effect of NO can lead to inhibition of viruses, and in fact, NO is considered one of the earliest antiviral responses of the host [41], whereas indirect effects include the regulation of inflammation and immune response [42]. NO also plays a key role in the generation of oxidized phospholipids [43], which can operate as potent immunomodulatory signals [44]. NO is necessary for the formation of several reactive oxygen and nitrogen species, including peryoxynitrite, dinitrogen trioxide, and nitrogen dioxide, which all can have an antiviral effect.…”

Crosstalk Between Intestinal Serotonergic System and Pattern Recognition Receptors on the Microbiota–Gut–Brain Axis

“…Reduced in IBD (293,297) Increased in IBS (248,302) Increased in UC (252) and in CD (293) Reduced in CD (252,298) Increased in Parkinson's disease (259) Increased in Alzheimer's disease (300) Decreased in autism spectrum disorder (301) Decreased in bipolar disorder (258) Increases 5-HT levels (232) Correlated with levels of serotonin (303) Veillonellaceae Increased in IBS (304,305) Increased in IBD (305,306) Increased in UC and CD (252) Decreased in autism spectrum disorder (256) Correlated with increased levels of serotonin (307) Lactobacillaceae Increased in IBS (248) Increased in IBD (297) Decreased in IBD (Lactobacillus) (250) Increased in CD and reduced in UC (252) Increased in Parkinson's disease (253,255,308) Decreased in Alzheimer's disease (251) Increased in Alzheimer's disease (300) Increased in autism spectrum disorder (257) Decreases TPH1, 5-THR 3 and 5-HTR 4 expression; and increases SERT expression…”

“…Decreased in Parkinson's disease (259) Increased in autism spectrum disorder (256,257) Correlated with levels of serotonin (303) Prevotellaceae Decreased in IBS (248) Increased in IBS (304) Increased in IBD (326) Increased in UC and CD (252) Decreased in Parkinson's disease (254,327) Decreased in autism spectrum disorder (256,321) Proteobacteria Enterobacteriaceae Increased in IBS (302) Increased in IBD (292,306) Increased in UC and CD (252) Increased in Parkinson's disease (328) Increased in Alzheimer's disease (300) Increased in autism spectrum disorder (257) Decreases 5-HT and SERT protein (329) Increase 5-HT bioavailability (330) Increases EC cells (331) Serotonin-producing bacterial strains (Escherichia coli K-12) insufficient, and novel studies have indicated that more treatments addressing innate immunity should be carried out. In this context, several studies have indicated that TLR (353) and NLR (354) modulation may help in the treatment of these chronic pathologies.…”

Epilipidomics platform for holistic profiling of oxidized complex lipids in blood plasma of obese individuals

“…Oxidized lipids have been shown to accumulate in apoptotic cells as well as microsomes released by activated or dying cells, and are generally associated with inflammatory responses, mediated mainly via the innate immune system 2 . Inflammation modulating potential of oxidized lipids is attributed to their recognition by and thus activation of a wide range of pattern recognition receptors including macrophage scavenger receptors, Toll-like receptors, CD36, and C reactive protein 9 . Moreover, oxidized lipids and their protein adducts can be recognized by natural IgM antibodies and thus sequestered from the circulation 5 .…”

“…Both enzymatic (via action of lipoxygenase, and cytochrome P450 systems 11,12 ) and non-enzymatic (via free radical driven lipid peroxidation 13,14 ) systems are proposed to contribute to the accumulation of oxidized lipids. Overall, an increasing body of evidence allows to propose that action of oxidized complex lipids is context dependent and their bioactivities might be manifested either in adaptive or pathological manner 9,11 . Understanding the underlying regularities in epilipidomics patterns would require holistic mapping of oxidized lipids in different conditions in a variety of biological matrices.…”