scholarly journals Pseudomonas aeruginosa Planktonic- and Biofilm-Conditioned Media Elicit Discrete Metabolic Responses in Human Macrophages

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2260
Author(s):  
Amanda Fuchs ◽  
Isaac Miller ◽  
Sage Schiller ◽  
Mary Ammons ◽  
Brian Eilers ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Inositol Phosphate ◽  
Human Monocyte ◽  
Innate Immune ◽  
Conditioned Media ◽  
Glycerol Metabolism ◽  
Adaptive Immune ◽  
Inositol Phosphate Metabolism ◽  
Microbial Products ◽  
Secretory Products

Macrophages (MΦs) are prevalent innate immune cells, present throughout human bodily tissues where they orchestrate innate and adaptive immune responses to maintain cellular homeostasis. MΦs have the capacity to display a wide array of functional phenotypes due to different microenvironmental cues, particularly soluble bacterial secretory products. Recent evidence has emerged demonstrating that metabolism supports MΦ function and plasticity, in addition to energy and biomolecular precursor production. In this study, 1D 1H-NMR-based metabolomics was used to identify the metabolic pathways that are differentially altered following primary human monocyte-derived MΦ exposure to P. aeruginosa planktonic- and biofilm-conditioned media (PCM and BCM). Metabolic profiling of PCM- and BCM-exposed MΦs indicated a significant increase in glycolytic metabolism, purine biosynthesis, and inositol phosphate metabolism. In addition, these metabolic patterns suggested that BCM-exposed MΦs exhibit a hyperinflammatory metabolic profile with reduced glycerol metabolism and elevated catabolism of lactate and amino acids, relative to PCM-exposed MΦs. Altogether, our study reveals novel findings concerning the metabolic modulation of human MΦs after exposure to secretory microbial products and contributes additional knowledge to the field of immunometabolism in MΦs.

scholarly journals Quantitative 1H NMR Metabolomics Reveal Distinct Metabolic Adaptations in Human Macrophages Following Differential Activation

Metabolites ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 248 ◽  
Author(s):  
Amanda L. Fuchs ◽  
Sage M. Schiller ◽  
Wyatt J. Keegan ◽  
Mary Cloud B. Ammons ◽  
Brian Eilers ◽  
...  
Keyword(s):  
1H Nmr ◽  
Metabolic Pathways ◽  
De Novo ◽  
Metabolic Activation ◽  
Human Monocyte ◽  
Acid Fermentation ◽  
Activation Markers ◽  
Adaptive Immune ◽  
Metabolic Adaptations ◽  
Additional Support

Macrophages (MΦs) are phagocytic immune cells that are found in nearly all human tissues, where they modulate innate and adaptive immune responses, thereby maintaining cellular homeostasis. MΦs display a spectrum of functional phenotypes as a result of microenvironmental and stress-induced stimuli. Evidence has emerged demonstrating that metabolism is not only crucial for the generation of energy and biomolecular precursors, but also contributes to the function and plasticity of MΦs. Here, 1D 1H NMR-based metabolomics was employed to identify metabolic pathways that are differentially modulated following primary human monocyte-derived MΦ activation with pro-inflammatory (M1) or anti-inflammatory (M2a) stimuli relative to resting (M0) MΦs. The metabolic profiling of M1 MΦs indicated a substantial increase in oxidative stress as well as a decrease in mitochondrial respiration. These metabolic profiles also provide compelling evidence that M1 MΦs divert metabolites from de novo glycerophospholipid synthesis to inhibit oxidative phosphorylation. Furthermore, glycolysis and lactic acid fermentation were significantly increased in both M1 and M2a MΦs. These metabolic patterns highlight robust metabolic activation markers of MΦ phenotypes. Overall, our study generates additional support to previous observations, presents novel findings regarding the metabolic modulation of human MΦs following activation, and contributes new knowledge to the rapidly evolving field of immunometabolism.

scholarly journals Comparison of gut microbiota structure and Actinobacteria abundances in healthy young adults and elderly subjects: a pilot study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jun Li ◽  
Haiyan Si ◽  
Haitao Du ◽  
Hongxia Guo ◽  
Huanqin Dai ◽  
...  
Keyword(s):  
Young Adults ◽  
Gut Microbiota ◽  
Metabolic Pathways ◽  
Inositol Phosphate ◽  
Species Abundance ◽  
Alpha Diversity ◽  
Elderly Subjects ◽  
Inositol Phosphate Metabolism ◽  
Potential Association ◽  
Young Subjects

Abstract Background The aim was to determine the potential association of the gut microbiota composition, especially the abundance of Actinobacteria, as well as the differentiation of functional and resistance genes with age (young adults vs elderly subjects) in China. Results The patterns of relative abundance of all bacteria isolated from fecal samples differed between young adults and elderly subjects, but the alpha diversity (Chao1 P = 0.370, Shannon P = 0.560 and Simpson P = 0.270) and beta diversity (ANOSIM R = 0.031, P = 0.226) were not significantly different. There were 3 Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways (carbon metabolism, inositol phosphate metabolism, and sesquiterpenoid and triterpenoid biosynthesis) and 7 antibiotic resistant genes (ARGs) (macrolide lincosamide-streptogramin B (MLSB), tetracycline, aminoglycoside, sulfonamide, fosmidomycin, lincomycin, and vancomycin) that showed significant differences between the 2 groups (all P < 0.05). The abundance of Actinomycetes was enriched (about 2.4-fold) in young adults. Bifidobacteria dominated in both young adults and elderly subjects, with overall higher abundances in young adults (P > 0.05). Only the Bifidobacterium_dentium species showed significant differences between the 2 groups (P = 0.013), with a higher abundance in elderly subjects but absent in young adults. Conclusions The present study revealed that there were 3 KEGG metabolic pathways and 7 ARGs as well as enhanced Bifidobacterium_dentium species abundance in elderly compared to young subjects.

Phytate as a phosphorus nutrient with impacts on iron stress-related gene expression for phytoplankton: insights from diatom Phaeodactylum tricornutum

2021 ◽  
Author(s):  
Jiashun Li ◽  
Kaidian Zhang ◽  
Xin Lin ◽  
Ling Li ◽  
Senjie Lin
Keyword(s):  
Metabolic Pathways ◽  
Phaeodactylum Tricornutum ◽  
Molecular Mechanisms ◽  
Inositol Phosphate ◽  
Organic Phosphorus ◽  
Sole Source ◽  
Systematic Investigation ◽  
Cellular Processes ◽  
Inositol Phosphate Metabolism ◽  
Stress Signals

Phytoplankton have evolved a capability to acquire phosphorus (P) from dissolved organic phosphorus (DOP) since the preferred form, dissolved inorganic phosphate (DIP, or Pi), is often limited in parts of the ocean. Phytic acid (PA) is abundantly synthesized in plants and rich in excreta of animals, potentially enriching the DOP pool in coastal oceans. However, whether and how PA may be used by phytoplankton are poorly understood. Here, we investigated PA utilization and underlying metabolic pathways in the diatom model Phaeodactylum tricornutum . The physiological results showed that P. tricornutum could utilize PA as a sole source of P nutrient to support growth. Meanwhile, the replacement of PA for DIP also caused changes in multiple cellular processes such as inositol phosphate metabolism, photosynthesis, and signal transduction. These results suggest that PA is bioavailable to P. tricornutum and can directly participate the metabolic pathways of PA-grown cells. However, our data showed that the utilization of PA was markedly less efficient than that of DIP, and PA-grown cells exhibited P and iron (Fe) nutrient stress signals. Implicated in these findings is the potential of complicated responses of phytoplankton to an ambient DOP species, which calls for more systematic investigation. IMPORTANCE PA is abundant in plants, and cannot be digested by non-ruminant animals. Hence, it is potentially a significant component of the DOP pool in the coastal waters. Despite the potential importance, there is little information about its bioavailability to phytoplankton as a source of P nutrient and if so what molecular mechanisms are involved. In this study, we found that part of PA could be utilized by the diatom P. tricornutum to support growth, and another portion of PA can act as a substrate directly participating in various metabolism pathways and cellular processes. However, our physiological and transcriptomic data show that PA-grown cells still exhibited signs of P stress and potential Fe stress. These results have significant implications in phytoplankton P nutrient ecology and provide a novel insight into multi-faceted impacts of DOP utilization on phytoplankton nutrition and metabolism.

scholarly journals The Role of Cell Metabolism in Innate Immune Memory

2020 ◽  
pp. 1-9
Author(s):  
Anaisa Valido Ferreira ◽  
Jorge Domiguéz-Andrés ◽  
Mihai Gheorghe Netea
Keyword(s):  
Metabolic Pathways ◽  
Tricarboxylic Acid Cycle ◽  
Cell Metabolism ◽  
Innate Immune ◽  
Immune Memory ◽  
Functional Changes ◽  
Trained Immunity ◽  
Health And Disease

Immunological memory is classically attributed to adaptive immune responses, but recent studies have shown that challenged innate immune cells can display long-term functional changes that increase nonspecific responsiveness to subsequent infections. This phenomenon, coined <i>trained immunity</i> or <i>innate immune memory</i>, is based on the epigenetic reprogramming and the rewiring of intracellular metabolic pathways. Here, we review the different metabolic pathways that are modulated in trained immunity. Glycolysis, oxidative phosphorylation, the tricarboxylic acid cycle, amino acid, and lipid metabolism are interplaying pathways that are crucial for the establishment of innate immune memory. Unraveling this metabolic wiring allows for a better understanding of innate immune contribution to health and disease. These insights may open avenues for the development of future therapies that aim to harness or dampen the power of the innate immune response.

scholarly journals Role of the Innate Immunity Signaling Pathway in the Pathogenesis of Sjögren’s Syndrome

2021 ◽  
Vol 22 (6) ◽  
pp. 3090
Author(s):  
Toshimasa Shimizu ◽  
Hideki Nakamura ◽  
Atsushi Kawakami
Keyword(s):  
Immune Responses ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Innate Immune ◽  
Type I ◽  
Type I Ifn ◽  
Adaptive Immune ◽  
Sjögren‘S Syndrome

Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by chronic inflammation of the salivary and lacrimal glands and extra-glandular lesions. Adaptive immune response including T- and B-cell activation contributes to the development of SS. However, its pathogenesis has not yet been elucidated. In addition, several patients with SS present with the type I interferon (IFN) signature, which is the upregulation of the IFN-stimulated genes induced by type I IFN. Thus, innate immune responses including type I IFN activity are associated with SS pathogenesis. Recent studies have revealed the presence of activation pattern recognition receptors (PRRs) including Toll-like receptors, RNA sensor retinoic acid-inducible gene I and melanoma differentiation-associated gene 5, and inflammasomes in infiltrating and epithelial cells of the salivary glands among patients with SS. In addition, the activation of PRRs via the downstream pathway such as the type I IFN signature and nuclear factor kappa B can directly cause organ inflammation, and it is correlated with the activation of adaptive immune responses. Therefore, this study assessed the role of the innate immune signal pathway in the development of inflammation and immune abnormalities in SS.

scholarly journals Innate and Adaptive Immune Genes Associated with MERS-CoV Infection in Dromedaries

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1291
Author(s):  
Sara Lado ◽  
Jean P. Elbers ◽  
Martin Plasil ◽  
Tom Loney ◽  
Pia Weidinger ◽  
...  
Keyword(s):  
Immune Response ◽  
United Arab Emirates ◽  
Innate Immune ◽  
Disease Dynamics ◽  
Genetic Pathways ◽  
Immune Genes ◽  
Adaptive Immune ◽  
Potential Association ◽  
Host Genetic ◽  
Human Infections

The recent SARS-CoV-2 pandemic has refocused attention to the betacoronaviruses, only eight years after the emergence of another zoonotic betacoronavirus, the Middle East respiratory syndrome coronavirus (MERS-CoV). While the wild source of SARS-CoV-2 may be disputed, for MERS-CoV, dromedaries are considered as source of zoonotic human infections. Testing 100 immune-response genes in 121 dromedaries from United Arab Emirates (UAE) for potential association with present MERS-CoV infection, we identified candidate genes with important functions in the adaptive, MHC-class I (HLA-A-24-like) and II (HLA-DPB1-like), and innate immune response (PTPN4, MAGOHB), and in cilia coating the respiratory tract (DNAH7). Some of these genes previously have been associated with viral replication in SARS-CoV-1/-2 in humans, others have an important role in the movement of bronchial cilia. These results suggest similar host genetic pathways associated with these betacoronaviruses, although further work is required to better understand the MERS-CoV disease dynamics in both dromedaries and humans.

scholarly journals Impact of cigarette versus electronic cigarette aerosol conditioned media on aortic endothelial cells in a microfluidic cardiovascular model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Om Makwana ◽  
Gina A. Smith ◽  
Hannah E. Flockton ◽  
Gary P. Watters ◽  
Frazer Lowe ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Human Monocyte ◽  
Conditioned Media ◽  
Electronic Cigarette ◽  
Microfluidic Channels ◽  
Adhesion Assay ◽  
Monocyte Adhesion ◽  
Aortic Endothelial Cells ◽  
Aortic Endothelial

AbstractAtherosclerosis is a complex process involving progressive pathological events, including monocyte adhesion to the luminal endothelial surface. We have developed a functional in vitro adhesion assay using BioFlux microfluidic technology to investigate THP-1 (human acute monocytic leukaemia cell) monocyte adhesion to human aortic endothelial cells (HAECs). The effect of whole smoke conditioned media (WSCM) generated from University of Kentucky reference cigarette 3R4F, electronic cigarette vapour conditioned media (eVCM) from an electronic nicotine delivery system (ENDS) product (Vype ePen) and nicotine on monocyte adhesion to HAECs was evaluated. Endothelial monolayers were grown in microfluidic channels and exposed to 0–1500 ng/mL nicotine or nicotine equivalence of WSCM or eVCM for 24 h. Activated THP-1 cells were perfused through the channels and a perfusion, adhesion period and wash cycle performed four times with increasing adhesion period lengths (10, 20, 30 and 40 min). THP-1 cell adhesion was quantified by counting adherent cells. WSCM induced dose-dependent increases in monocyte adhesion compared to vehicle control. No such increases were observed for eVCM or nicotine. Adhesion regulation was linked to increased ICAM-1 protein expression. Staining of ICAM-1 in HAECs and CD11b (MAC-1) in THP-1 cells demonstrated adhesion molecule co-localisation in BioFlux plates. The ICAM-1 adhesion response to WSCM was downregulated by transfecting HAECs with ICAM-1 siRNA. We conclude that the BioFlux system is able to model human monocyte adhesion to primary human endothelial cells in vitro and WSCM drives the greatest increase in monocyte adhesion via a mechanism involving endothelial ICAM-1 expression.

scholarly journals Effects of Staphylococcus aureus Bacteriophage K on Expression of Cytokines and Activation Markers by Human Dendritic Cells In Vitro

Viruses ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 617 ◽  
Author(s):  
Helen Freyberger ◽  
Yunxiu He ◽  
Amanda Roth ◽  
Mikeljon Nikolich ◽  
Andrey Filippov
Keyword(s):  
Staphylococcus Aureus ◽  
Dendritic Cells ◽  
Inflammatory Response ◽  
Adaptive Immune Response ◽  
Human Monocyte ◽  
Activation Markers ◽  
Mhc I ◽  
Adaptive Immune ◽  
Human Dendritic Cells

A potential concern with bacteriophage (phage) therapeutics is a host-versus-phage response in which the immune system may neutralize or destroy phage particles and thus impair therapeutic efficacy, or a strong inflammatory response to repeated phage exposure might endanger the patient. Current literature is discrepant with regard to the nature and magnitude of innate and adaptive immune response to phages. The purpose of this work was to study the potential effects of Staphylococcus aureus phage K on the activation of human monocyte-derived dendritic cells. Since phage K acquired from ATCC was isolated around 90 years ago, we first tested its activity against a panel of 36 diverse S. aureus clinical isolates from military patients and found that it was lytic against 30/36 (83%) of strains. Human monocyte-derived dendritic cells were used to test for an in vitro phage-specific inflammatory response. Repeated experiments demonstrated that phage K had little impact on the expression of pro- and anti-inflammatory cytokines, or on MHC-I/II and CD80/CD86 protein expression. Given that dendritic cells are potent antigen-presenting cells and messengers between the innate and the adaptive immune systems, our results suggest that phage K does not independently affect cellular immunity or has a very limited impact on it.

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