Lipidomic alterations of in vitro macrophage infection by L. infantum and L. amazonensis

Negrão, Fernanda; Abánades, Daniel R.; Jaeeger, Caroline F.; Rocha, Daniele F. O.; Belaz, K. R. A.; Giorgio, Selma; Eberlin, Marcos N.; Angolini, Célio F. F.

doi:10.1039/c7mb00381a

Cited by 14 publications

(14 citation statements)

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“…PCs were also increased in the infected footpad ( Table 3 and Table 4 , Figure 3 ). This increase concurs with prior reports of elevated lysophosphatidylcholine (LPC) and PCs in infected macrophages in vitro [ 23 , 28 ]. Concordance between infection models supports our approach and translatability of results.…”

Section: Discussionsupporting

confidence: 92%

“…In addition, changes in the host plasma metabolite abundance, including pyruvate, taurine and N -acetylglutamine, can serve as an indicator of response to CL treatment [ 19 ]. Several studies previously investigated Leishmania and host metabolism during in vitro macrophage infection [ 20 , 21 , 22 , 23 ], or in amastigotes purified from mouse granulomatous lesions [ 24 ], but there is still a lack of knowledge of host metabolic responses during in vivo infection.…”

Section: Discussionmentioning

confidence: 99%

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Dysregulation of Glycerophosphocholines in the Cutaneous Lesion Caused by Leishmania major in Experimental Murine Models

et al. 2021

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Cutaneous leishmaniasis (CL) is the most common disease form caused by a Leishmania parasite infection and considered a neglected tropical disease (NTD), affecting 700,000 to 1.2 million new cases per year in the world. Leishmania major is one of several different species of the Leishmania genus that can cause CL. Current CL treatments are limited by adverse effects and rising resistance. Studying disease metabolism at the site of infection can provide knowledge of new targets for host-targeted drug development. In this study, tissue samples were collected from mice infected in the ear or footpad with L. major and analyzed by untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS). Significant differences in overall metabolite profiles were noted in the ear at the site of the lesion. Interestingly, lesion-adjacent, macroscopically healthy sites also showed alterations in specific metabolites, including selected glycerophosphocholines (PCs). Host-derived PCs in the lower m/z range (m/z 200–799) showed an increase with infection in the ear at the lesion site, while those in the higher m/z range (m/z 800–899) were decreased with infection at the lesion site. Overall, our results expanded our understanding of the mechanisms of CL pathogenesis through host metabolism and may lead to new curative measures against infection with Leishmania.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Dysregulation of Glycerophosphocholines in the Cutaneous Lesion Caused by Leishmania major in Experimental Murine Models

et al. 2021

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“…Many of the bands in the spectral region around 1350 cm -1 , which is obvious in many of the vacuole spectra, are assigned to different protein and sugar components, as well as to inositol [235], likely reflecting the presence of modified lipids and proteins. In Leishmania, glycoinositol-phospholipids have been shown to be an abundant molecular class [255,256], in addition to lipids that have an additional ether double bond at the sn-1 position [257]. In addition to the high abundance of lipids and glycosylated lipids, distinct vibrational modes of cholesterol as discussed above, and also of ergosterol are observed.…”

Section: Sers Spectra From Leishmania Infected Cellsmentioning

confidence: 94%

Nano-bio interactions as characterized by SERS: The interaction of liposomes with gold nanostructures is highly dependent on lipid composition and charge

Živanović

Kneipp

2019

Plasmonics in Biology and Medicine XVI

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Lysosomes are organelles of great importance for degradation processes of membranes and proteins in cells, and play a crucial role in cellular homeostasis. They can also serve as a potential target for cancer therapy. Monitoring lysosomes that accumulate lipids with sufficient temporal and spatial resolution still represents a considerable challenge. This thesis focuses on the development of surface-enhanced Raman scattering (SERS) as a method to monitor intact lysosomes, in particular regarding the influence of drug molecules that interfere with lipid metabolism. In order to evaluate the potential of SERS for studying lysosomal biology in live cells, the interactions between tricyclic antidepressants and acid sphingomyelinase (ASM) were studied. First, model systems were investigated. In particular, the interactions between the antidepressant molecules desipramine, imipramine, and amitriptyline, and gold and silver nanoparticles were characterized by SERS and surface-enhanced hyper-Raman scattering. The combined one-and two-photon approach showed that molecules interact with the surface of gold nanoparticles via their ring moiety and the methylaminopropyl side chain. As a model system of the lipid-rich environment in the lysosomes, composites of liposome and gold nanoparticles were prepared and studied by SERS and cryogenic electron microscopy. The SERS spectra are characteristic of the vesicles' lipid composition, and the data identify the lipids' polar head as the main contact site with the nanoparticles. The interactions between the antidepressants and the lysosomes were studied in the fibroblast cell line 3T3 by SERS and complementary methods. Apart from the collection of SERS spectra from the live cells, the cellular ultrastructure was characterized by transmission electron microscopy and cryo X-ray tomography. The ultrastructural data show an accumulation of lipids in the lysosomes, induced by the inhibition of ASM by the antidepressant molecules. In agreement with the SERS spectra Obtaining a PhD was an exciting journey, and there are many people to whom I owe a debt of gratitude. First, I would like to express my sincere gratitude to my PhD supervisors Prof.Dr. Janina Kneipp and Prof. Dr. Christoph Arenz for the opportunity of working with them and their continuous support during my PhD research. Most of all, I want to express my deepest appreciation to Prof. Dr. Janina Kneipp from whom I learned a lot during these four years, for all the scientific and non-scientific discussions, the positive attitude towards research, for helping me develop ideas and see things from a different perspective; and especially, for all work together before deadlines. I could not have imagined having a better and more understanding mentor for my PhD.

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“…Recent transcriptomics, lipidomics, , and proteomics − studies have demonstrated how different species of Leishmania modulate the host in order to survive and proliferate . Our most recent studies , compared an inflammation model to different species of Leishmania spp.…”

mentioning

confidence: 99%

Tandem Mass Tag Proteomic Analysis of in Vitro and in Vivo Models of Cutaneous Leishmaniasis Reveals Parasite-Specific and Nonspecific Modulation of Proteins in the Host

et al. 2019

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Cutaneous leishmaniasis, the most common form of leishmaniasis, is endemic in several regions of the world, and if not treated properly, it can cause disfiguring scars on the skin. Leishmania spp. infection causes an inflammatory response in its host, and it modulates the host metabolism differently depending on the Leishmania species. Since Leishmania spp. has begun to develop resistance against current therapies, we believe efforts to identify new possibilities for treatment are critical for future control of the disease. Proteomics approaches such as isobaric labeling yield accurate relative quantification of protein abundances and, when combined with chemometrics/statistical analysis, provide robust information about protein modulation across biological conditions. Using a mass spectrometry-based proteomics approach and tandem mass tag labeling, we have investigated protein modulation in murine macrophages (in vitro model) and skin biopsies after exposure to Leishmania spp. (in vivo murine model). Infections induced by L. amazonensis (endemic in the New World) and L. major (endemic in the Old World) were compared to an inflammation model to search for Leishmania-specific and nonspecific protein modulation in the host. After protein extracts obtained from in vitro and in vivo experiments were digested, the resulting peptides were labeled with isobaric tags and analyzed by liquid chromatography-MS (LC-MS). Several proteins that were found to be changed upon infection with Leishmania spp. provide interesting candidates for further investigation into disease mechanism and development of possible immunotherapies.

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Lipidomic alterations of in vitro macrophage infection by L. infantum and L. amazonensis

Cited by 14 publications

References 30 publications

Dysregulation of Glycerophosphocholines in the Cutaneous Lesion Caused by Leishmania major in Experimental Murine Models

Dysregulation of Glycerophosphocholines in the Cutaneous Lesion Caused by Leishmania major in Experimental Murine Models

Nano-bio interactions as characterized by SERS: The interaction of liposomes with gold nanostructures is highly dependent on lipid composition and charge

Tandem Mass Tag Proteomic Analysis of in Vitro and in Vivo Models of Cutaneous Leishmaniasis Reveals Parasite-Specific and Nonspecific Modulation of Proteins in the Host

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