Lipidomic analysis of immune activation in equine leptospirosis and Leptospira-vaccinated horses.

Currently available diagnostic assays for leptospirosis cannot differentiate vaccine from infection serum antibody. Several leptospiral proteins that are upregulated during infection have been described, but their utility as a diagnostic marker is still unclear. In this study, we undertook a lipidomics approach to determine if there are any differences in the serum lipid profiles of horses naturally infected with pathogenic Leptospira spp. and horses vaccinated against a commercially available bacterin. Utilizing a high-resolution mass spectrometry serum lipidomics analytical platform, we demonstrate that cyclic phosphatidic acids, diacylglycerols, and hydroperoxide oxidation products of choline plasmalogens are elevated in the serum of naturally infected as well as vaccinated horses. Other lipids of interest were triacylglycerols that were only elevated in the serum of infected horses and sphingomyelins that were increased only in the serum of vaccinated horses. This is the first report looking at the equine serum lipidome during leptospiral infection and vaccination.

Serum lipidomics of bovine paratuberculosis: Disruption of choline-containing glycerophospholipids and sphingolipids.

OBJECTIVES: Bovine paratuberculosis is a devastating infection with Mycobacterium avium subspecies paratuberculosis that ultimately results in death from malnutrition. While the infection is characterized by a long (2-4 years) subclinical phase with immune activation, ultimately host defense mechanisms fail and the bacteria spread from the small intestine to other organs. Since both the gastrointestinal tract and liver are essential for the biosynthesis of structural glycerophospholipids, we investigated the circulating levels of these lipids in field infections and experimentally infected cattle. METHODS: Serum lipidomics of control and M. avium subspecies paratuberculosis-infected cattle were performed utilizing high-resolution mass spectrometry. RESULTS: In M. avium subspecies paratuberculosis-positive cattle, demonstrating clinical signs, we monitored large decreases in the levels of circulating phosphocholine-containing lipids. These included phosphatidylcholines, choline plasmalogens, and sphingomyelins. Next, we monitored the time course of these lipid alterations in experimentally infected calves and found that altered lipid levels were only detected in cattle with clinical signs of infection. CONCLUSIONS: Our data indicate that altered availability of choline-containing lipids occurs late in the disease process and is most likely a result of malnutrition and altered biosynthetic capacities of the liver and gastrointestinal tract. Alterations in the bioavailability of these critical structural lipids presumably contributes to the demise of M. avium subspecies paratuberculosis-infected cattle. In light of increasing concern that M. avium subspecies paratuberculosis may be a zoonotic bacterium that contributes to the development of Crohn's disease and multiple sclerosis, our data also have human clinical relevance.