Metabolic characterization of Leishmania major infection in activated and nonactivated macrophages.
Infection with Leishmania spp. can lead to a range of symptoms in the affected individual, depending on underlying immune-metabolic processes. The macrophage activation state hereby plays a key role. Whereas the l-arginine pathway has been described in detail as the main biochemical process responsible for either nitric oxide mediated parasite killing (classical activation) or amplification of parasite replication (alternative activation), we were interested in a wider characterization of metabolic events in vitro. We therefore assessed cell growth medium, parasite extract, and intra- and extracellular metabolome of activated and nonactivated macrophages, in presence and absence of Leishmania major. A metabolic profiling approach was applied combining 1H NMR spectroscopy with multi- and univariate data treatment. Metabolic changes were observed along both conditional axes, that is, infection state and macrophage activation, whereby significantly higher levels of potential parasite end products were found in parasite exposed samples including succinate, acetate, and alanine, compared to uninfected macrophages. The different macrophage activation states were mainly discriminated by varying glucose consumption. The presented profiling approach allowed us to obtain a metabolic snapshot of the individual biological compartments in the assessed macrophage culture experiments and represents a valuable read out system for further multiple compartment in vitro studies.
Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, South Kensington, London SW7 2AZ, United Kingdom.
Sabrina D
SD
Lamour
Beak-San
BS
Choi
Hector C
HC
Keun
Ingrid
I
Müller
Jasmina
J
Saric
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002457:Cell Extracts / Q000737:chemistry; D002478:Cells, Cultured; D005260:Female; D005947:Glucose / Q000378:metabolism; D006790:Host-Parasite Interactions; D016018:Least-Squares Analysis; D018320:Leishmania major / Q000502:physiology*; D007896:Leishmaniasis / Q000378:metabolism* / Q000469:parasitology; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism* / Q000469:parasitology / Q000502:physiology; D055442:Metabolome; D051379:Mice; D008807:Mice, Inbred BALB C; D015999:Multivariate Analysis; D025341:Principal Component Analysis
D015415:Biomarkers; D002457:Cell Extracts; D005947:Glucose