Cytokines and metabolic regulation: A framework of bidirectional influences affecting Leishmania infection

Bodhale, Neelam; Ohms, Mareike; Ferreira, Carolina; Mesquita, Inês; Mukherjee, Arkajyoti; André, Sónia; Sarkar, Arup; Estaquier, Jérǒme; Laskay, Tamás; Saha, Bhaskar; Silvestre, Ricardo

doi:10.1016/j.cyto.2020.155267

Cited by 11 publications

(6 citation statements)

References 206 publications

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“…An example is the glucose and lipid metabolism, which is known to be shifted during a high production of cytokines TNF-α, IL-6, and IL-1β and during the entry, replication, and egress of the virus at/from the host cell. 42 , 44 − 46 In detail, glucose resistance is highlighted during the production of cytokines, while lipolysis and triglyceride synthesis are upregulated. Similarly, it is also known that viruses might alter the host cell metabolism on behalf of its replication, similar to the Walburg effect, widely studied in cancer models, also known as aerobic glycolysis.…”

Section: Discussionmentioning

confidence: 99%

“…This process triggers the immune system that relocates metabolic resources to start the production of antibodies and cytokines, looking for targeting viral particles and controlling the virus spreading. However, in SARS-CoV-2 virus infection, the release of the cytokines may be exaggerated, disrupting severe inflammations, mainly related to high production of interleukins (ILs), macrophage colony stimulating factors (M-CSFs), granulocyte colony stimulating factors (G-CSFs), and interferons (IFNs). − …”

Section: Discussionmentioning

confidence: 99%

“…As mentioned, to produce high concentrations of such proteins, the metabolism needs to adapt and relocate its resources, culminating in a metabolite concentration shift. An example is the glucose and lipid metabolism, which is known to be shifted during a high production of cytokines TNF-α, IL-6, and IL-1β and during the entry, replication, and egress of the virus at/from the host cell. ,− In detail, glucose resistance is highlighted during the production of cytokines, while lipolysis and triglyceride synthesis are upregulated. Similarly, it is also known that viruses might alter the host cell metabolism on behalf of its replication, similar to the Walburg effect, widely studied in cancer models, also known as aerobic glycolysis. , Compared to cancer cells, the virus’s replication is highly dependent on the availability of glucose and glutamine (carbon sources) and the tricarboxylic acid cycle (TCA) process.…”

Section: Discussionmentioning

confidence: 99%

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¹H qNMR-Based Metabolomics Discrimination of Covid-19 Severity

et al. 2022

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The coronavirus disease 2019 (Covid-19), which caused respiratory problems in many patients worldwide, led to more than 5 million deaths by the end of 2021. Experienced symptoms vary from mild to severe illness. Understanding the infection severity to reach a better prognosis could be useful to the clinics, and one study area to fulfill one piece of this biological puzzle is metabolomics. The metabolite profile and/or levels being monitored can help predict phenotype properties. Therefore, this study evaluated plasma metabolomes of 110 individual samples, 57 from control patients and 53 from recent positive cases of Covid-19 (IgM 98% reagent), representing mild to severe symptoms, before any clinical intervention. Polar metabolites from plasma samples were analyzed by quantitative 1 H NMR. Glycerol, 3-aminoisobutyrate, formate, and glucuronate levels showed alterations in Covid-19 patients compared to those in the control group (Tukey’s HSD p -value cutoff = 0.05), affecting the lactate, phenylalanine, tyrosine, and tryptophan biosynthesis and d -glutamine, d -glutamate, and glycerolipid metabolisms. These metabolic alterations show that SARS-CoV-2 infection led to disturbance in the energetic system, supporting the viral replication and corroborating with the severe clinical conditions of patients. Six polar metabolites (glycerol, acetate, 3-aminoisobutyrate, formate, glucuronate, and lactate) were revealed by PLS-DA and predicted by ROC curves and ANOVA to be potential prognostic metabolite panels for Covid-19 and considered clinically relevant for predicting infection severity due to their straight roles in the lipid and energy metabolism. Thus, metabolomics from samples of Covid-19 patients is a powerful tool for a better understanding of the disease mechanism of action and metabolic consequences of the infection in the human body and may corroborate allowing clinicians to intervene quickly according to the needs of Covid-19 patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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¹H qNMR-Based Metabolomics Discrimination of Covid-19 Severity

et al. 2022

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“…To understand the immune metabolic reprogramming during Leishmania infection, we also evaluated the release of arachidonic acid metabolites including leukotrienes and prostaglandins in infected peritoneal macrophages. In subversion by L. donovani infection, parasites utilize anti-inflammatory cytokines (TGF-β, IL-10) and arachidonic acid metabolites (predominantly prostaglandins) to survive inside macrophages ( Bodhale et al., 2020 ). Subsequently, we investigated that the release of prostaglandin was regulated by the cyclooxygenase (COX-2) pathway during L. donovani infection ( Figures 3A–B ).…”

Section: Discussionmentioning

confidence: 99%

Dynamicity in Host Metabolic Adaptation Is Influenced by the Synergistic Effect of Eugenol Oleate and Amphotericin B During Leishmania donovani Infection In Vitro

Kar

Jayaraman

Kumar

et al. 2021

Front. Cell. Infect. Microbiol.

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Immune metabolic adaptation in macrophages by intracellular parasites is recognized to play a crucial role during Leishmania infection. However, there is little accessible information about changes in a metabolic switch in L. donovani infected macrophages. In previous studies, we have reported on the anti-leishmanial synergic effect of eugenol oleate with amphotericin B. In the present study, we demonstrated that glycolytic enzymes were highly expressed in infected macrophages during combinatorial treatment of eugenol oleate (2.5 µM) and amphotericin B (0.3125 µM). Additionally, we found that the biphasic role in arachidonic acid metabolite, PGE2, and LTB4, is released during this treatment. In vitro data showed that COX-2 mediated PGE2 synthesis increased significantly (p<0.01) in infected macrophages. Not only was the level of prostaglandin synthesis decreased 4.38 fold in infected macrophages after treatment with eugenol oleate with amphotericin B. The mRNA expression of PTGES, MPGES, and PTGER4 were also moderately expressed in infected macrophages, and found to be decreased in combinatorial treatment. In addition, NOS2 expression was activated by the phosphorylation of p38MAPK when combination-treated macrophages were promoted to kill intracellular parasites. The findings of the present study indicate that the synergism between eugenol oleate and amphotericin B could play an important role in immune metabolism adaptation with a concomitant increase in host immune response against the intracellular pathogen, L. donovani.

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“…Metabolic reprogramming of Leishmania-infected macrophages promotes infection and immune evasion by lowering the capacity of the infected cells to induce effective immune responses [2][3][4][5]. Leishmania was shown to remodel host nutrient reserves by modulating the central nutrient-sensing pathways-AMPK, mTOR, and HIF-1α-to its own advantage [3,4,[6][7][8][9][10]. Glycolysis and glutaminolysis were shown to serve as major carbon sources for Leishmania-infected macrophages [2,4,11].…”

Section: Introductionmentioning

confidence: 99%

Intramacrophage lipid accumulation compromises T cell responses and is associated with impaired drug therapy against visceral leishmaniasis

Araújo,

Moreira,

Mesquita

et al. 2023

Immunology

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Under perturbing conditions such as infection with Leishmania, a protozoan parasite living within the phagosomes in mammalian macrophages, cellular and organellar structures, and metabolism are dynamically regulated for neutralizing the pressure of parasitism. However, how modulations of the host cell metabolic pathways support Leishmania infection remains unknown. Herein, we report that lipid accumulation heightens the susceptibility of mice to L. donovani infection and promotes resistance to first‐line anti‐leishmanial drugs. Despite being pro‐inflammatory, the in vitro generated uninfected lipid‐laden macrophages (LLMs) or adipose‐tissue macrophages (ATMs) display lower levels of reactive oxygen and nitrogen species. Upon infection, LLMs secrete higher IL‐10 and lower IL‐12p70 cytokines, inhibiting CD4+ T cell activation and Th1 response suggesting a key modulatory role for intramacrophage lipid accumulation in anti‐leishmanial host defence. We, therefore, examined this causal relationship between lipids and immunomodulation using an in vivo high‐fat diet (HFD) mouse model. HFD increased the susceptibility to L. donovani infection accompanied by a defective CD4+ Th1 and CD8+ T cell response. The white adipose tissue of HFD mice displays increased susceptibility to L. donovani infection with the preferential infection of F4/80+CD11b+CD11c+ macrophages with higher levels of neutral lipids reserve. The HFD increased resistance to a first‐line anti‐leishmanial drug associated with a defective adaptive immune response. These data demonstrate that the accumulation of neutral lipids contributes to susceptibility to visceral leishmaniasis hindering host‐protective immune response and reducing the efficacy of antiparasitic drug therapies.

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Cytokines and metabolic regulation: A framework of bidirectional influences affecting Leishmania infection

Cited by 11 publications

References 206 publications

¹H qNMR-Based Metabolomics Discrimination of Covid-19 Severity

¹H qNMR-Based Metabolomics Discrimination of Covid-19 Severity

Dynamicity in Host Metabolic Adaptation Is Influenced by the Synergistic Effect of Eugenol Oleate and Amphotericin B During Leishmania donovani Infection In Vitro

Intramacrophage lipid accumulation compromises T cell responses and is associated with impaired drug therapy against visceral leishmaniasis

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Cytokines and metabolic regulation: A framework of bidirectional influences affecting Leishmania infection

Cited by 11 publications

References 206 publications

1H qNMR-Based Metabolomics Discrimination of Covid-19 Severity

1H qNMR-Based Metabolomics Discrimination of Covid-19 Severity

Dynamicity in Host Metabolic Adaptation Is Influenced by the Synergistic Effect of Eugenol Oleate and Amphotericin B During Leishmania donovani Infection In Vitro

Intramacrophage lipid accumulation compromises T cell responses and is associated with impaired drug therapy against visceral leishmaniasis

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¹H qNMR-Based Metabolomics Discrimination of Covid-19 Severity

¹H qNMR-Based Metabolomics Discrimination of Covid-19 Severity