Metabolite Transporters as Regulators of Immunity

Weiss, Hauke J.; Angiari, Stefano

doi:10.3390/metabo10100418

Cited by 27 publications

(27 citation statements)

References 144 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An increasing number of evidence in the past decade has highlighted the role of solute carrier (SLC) transporters in shaping the immune responses by modulating the bioavailability of many metabolites, including amino acids and their derivatives ( 36 ). In this context we demonstrate here that, in Calu-3 bronchial epithelial cells and EpiAirway™ tissues, the induction of a pro-inflammatory phenotype by bacterial FLA-PA is associated with an upregulation of the expression and activity of SLC6A14 /ATB 0,+ transporter for cationic and neutral amino acids.…”

Section: Discussionmentioning

confidence: 99%

Flagellin From Pseudomonas Aeruginosa Stimulates ATB0,+ Transporter for Arginine and Neutral Amino Acids in Human Airway Epithelial Cells

et al. 2021

View full text Add to dashboard Cite

At present, the central role played by arginine in the modulation of the inflammatory cellular responses is well-recognized, and many pro-inflammatory stimuli are known to modulate the expression and activity of its transmembrane transporters. In this regard, we have addressed the effects of bacterial flagellin from Pseudomonas aeruginosa (FLA-PA) on the uptake of the amino acid in human epithelial respiratory cells. Among the arginine transporters, only ATB0,+, y+L, and y+ were operative in bronchial epithelial Calu-3 cells under control conditions; however, only the expression and activity of ATB0,+ were stimulated upon incubation with flagellin, whereas those of systems y+L and y+ were not stimulated. As a result, this induction, in turn, led to an increase in the intracellular content of arginine without making any change to its metabolic pathway. In addition, flagellin upregulated the amount of other amino acids substrates of ATB0,+, in particular, all the essential amino acids, such as valine, isoleucine, and leucine, along with the non-essential glutamine. At the molecular level, these effects were directly referable to the stimulation of a toll-like receptor-5 (TLR5) signaling pathway and to the induction of nuclear factor-κB (NF-κB) transcription factor. An induction of ATB0,+ expression has been observed also in EpiAirway™, a model of primary human normal tracheal-bronchial epithelial cells that mimics the in vitro pseudostratified columnar epithelium of the airways. In this tissue model, the incubation with flagellin is associated with the upregulation of messenger RNAs (mRNAs) for the chemokine IL-8 and for the cytokines IL-6 and interleukin-1β (IL-1β); as for the latter, a marked secretion in the extracellular medium was also observed due to the concomitant activation of caspase-1. The overall findings indicate that, in human respiratory epithelium, flagellin promotes cellular responses associating the increase of intracellular amino acids through ATB0,+ with the activation of the inflammasome. Given the role of the ATB0,+ transporter as a delivery system for bronchodilators in human airway epithelial cells, its induction under inflammatory conditions gains particular relevance in the field of respiratory pharmacology.

show abstract

Section: Discussionmentioning

confidence: 99%

Flagellin From Pseudomonas Aeruginosa Stimulates ATB0,+ Transporter for Arginine and Neutral Amino Acids in Human Airway Epithelial Cells

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Indeed, when analyzing the transcriptome of circulating immune cells, the top gene signature negatively associated with CRP was Oxidative Phosphorylation, with expression of many components of the ETC being downregulated in patients with high CRP. Furthermore, these changes were accompanied by increase mRNA expression of the glucose transporter SLC2A3 and the monocarboxylate transporter SLC16A3, which can be associated to activation of different immune cell subsets (Simpson et al, 2008; Weiss and Angiari, 2020). Dysregulation of mitochondrial metabolism is increasingly appreciated in COVID-19 (Burtscher et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

The COVIDome Explorer Researcher Portal

Sullivan

Galbraith

Kinning

et al. 2021

Preprint

View full text Add to dashboard Cite

COVID-19 pathology involves dysregulation of diverse molecular, cellular, and physiological processes. In order to expedite integrated and collaborative COVID-19 research, we completed multi-omics analysis of hospitalized COVID-19 patients including matched analysis of the whole blood transcriptome, plasma proteomics with two complementary platforms, cytokine profiling, plasma and red blood cell metabolomics, deep immune cell phenotyping by mass cytometry, and clinical data annotation. We refer to this multidimensional dataset as the COVIDome. We then created the COVIDome Explorer, an online researcher portal where the data can be analyzed and visualized in real time. We illustrate here the use of the COVIDome dataset through a multi-omics analysis of biosignatures associated with C-reactive protein (CRP), an established marker of poor prognosis in COVID-19, revealing associations between CRP levels and damage-associated molecular patterns, depletion of protective serpins, and mitochondrial metabolism dysregulation. We expect that the COVIDome Explorer will rapidly accelerate data sharing, hypothesis testing, and discoveries worldwide.

show abstract

“…Upon activation, DCs and macrophages undergo profound metabolic changes critical for biosynthesis and energy production ( 12 ). Lactate could also serve as a fuel source to produce energy by various cell types, including immune, cancer, and stromal cells ( 13 , 14 ). Like other cell types, APCs produce lactate under hypoxic conditions or by aerobic glycolysis.…”

Section: Lactate Metabolism and Transport In Dendritic Cells And Macrophagesmentioning

confidence: 99%

“…Lactate in the cell or extracellular space is transported across the plasma membrane by monocarboxylate transporters (MCTs) of the SLC16 solute carrier family, and they transport lactate by an H + -coupled transport mechanism ( 13 , 14 , 21 , 22 ). MCTs, prevent intracellular accumulation of lactate by removing excess lactate produced due to increased glycolytic activity ( 23 , 24 ).…”

Section: Lactate Metabolism and Transport In Dendritic Cells And Macrophagesmentioning

confidence: 99%

Lactate-Dependent Regulation of Immune Responses by Dendritic Cells and Macrophages

et al. 2021

View full text Add to dashboard Cite

For decades, lactate has been considered an innocuous bystander metabolite of cellular metabolism. However, emerging studies show that lactate acts as a complex immunomodulatory molecule that controls innate and adaptive immune cells’ effector functions. Thus, recent advances point to lactate as an essential and novel signaling molecule that shapes innate and adaptive immune responses in the intestine and systemic sites. Here, we review these recent advances in the context of the pleiotropic effects of lactate in regulating diverse functions of immune cells in the tissue microenvironment and under pathological conditions.

show abstract

Metabolite Transporters as Regulators of Immunity

Cited by 27 publications

References 144 publications

Flagellin From Pseudomonas Aeruginosa Stimulates ATB0,+ Transporter for Arginine and Neutral Amino Acids in Human Airway Epithelial Cells

Flagellin From Pseudomonas Aeruginosa Stimulates ATB0,+ Transporter for Arginine and Neutral Amino Acids in Human Airway Epithelial Cells

The COVIDome Explorer Researcher Portal

Lactate-Dependent Regulation of Immune Responses by Dendritic Cells and Macrophages

Contact Info

Product

Resources

About