In response to infection, macrophages adapt their metabolism rapidly to enhance glycolysis and fuel specialized antimicrobial effector functions. Here we show that fungal melanin is an essential molecule required for the metabolic rewiring of macrophages during infection with the fungal pathogen Aspergillus fumigatus. Using pharmacological and genetic tools, we reveal a molecular link between calcium sequestration by melanin inside the phagosome and induction of glycolysis required for efficient innate immune responses. By remodeling the intracellular calcium machinery and impairing signaling via calmodulin, melanin drives an immunometabolic signaling axis towards glycolysis with activation of hypoxia-inducible factor 1 subunit alpha (HIF-1α) and phagosomal recruitment of mammalian target of rapamycin (mTOR). These data demonstrate a pivotal mechanism in the immunometabolic regulation of macrophages during fungal infection and highlight the metabolic repurposing of immune cells as a potential therapeutic strategy.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210971 | PMC |
| http://dx.doi.org/10.1038/s41467-020-16120-z | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
F-box protein Fbx23 acts as a transcriptional coactivator to recognize and activate transcription factor Ace1.
PLoS Genet
January 2025
National Glycoengineering Research Center, Shandong University, Qingdao, China.
Protein ubiquitination is usually coupled with proteasomal degradation and is crucial in regulating protein quality. The E3 ubiquitin-protein ligase SCF (Skp1-Cullin-F-box) complex directly recognizes the target substrate via interaction between the F-box protein and the substrate. F-box protein is the determinant of substrate specificity.
View Article and Find Full Text PDFUnveiling the multifaceted potential of amyloid fibrils: from pathogenic myths to biotechnological marvels.
Biophys Rev
December 2024
Amity Institute of Molecular Medicine and Stem Cell Research, Amity University Uttar Pradesh, 201313 Noida, India.
Amyloid fibrils, historically stigmatized due to their association with diseases like Alzheimer's and Parkinson's, are now recognized as a distinct class of functional proteins with extraordinary potential. These highly ordered, cross-β-sheet protein aggregates are found across all domains of life, playing crucial physiological roles. In bacteria, functional amyloids like curli fibers are essential for surface adhesion, biofilm formation, and viral DNA packaging.
View Article and Find Full Text PDFInhibition of Melanin Synthesis and Inflammation by Exosomes Derived from DB-14 Isolated from Flower.
J Microbiol Biotechnol
January 2025
Department of Pharmaceutical Engineering & Biotechnology, Sunmoon University, Chungnam 31460, Republic of Korea.
is a lactic acid bacteria found in fermented products. In our previous study, was isolated from flowers, and its acid tolerance and antibacterial properties were thoroughly investigated. This study focuses on the inhibition of melanin synthesis and inflammation of exosomes derived from .
View Article and Find Full Text PDFSuppression of mycotoxins production and efficient chelation of heavy metals using natural melanin originated from Aspergillus flavus and Aspergillus carbonarius.
BMC Biotechnol
January 2025
Department of Botany and Microbiology, Faculty of Science, Zagazig University, Zagazig, Sharkia, 44519, Egypt.
Background: This study employed melanin synthesized by Aspergillus flavus and Aspergillus carbonarius to inhibit the production of mycotoxins and bioremediation of heavy metals (HMs).
Methods: First, twenty fungal isolates were obtained from soil samples, and were evaluated to produce melanin. The melanin of the most potent producers has undergone several confirmatory experiments, including, Dihydroxyphenylalanine (DOPA)-inhibitor-kojic acid pathway detection, High-performance liquid chromatography (HPLC), Fourier-transform infrared (FTIR) and Nuclear magnetic resonance (NMR).
Mechanisms of regulated cell death during plant infection by the rice blast fungus Magnaporthe oryzae.
Cell Death Differ
January 2025
The Sainsbury Laboratory, University of East Anglia, Norwich, UK.
Fungi are the most important group of plant pathogens, responsible for many of the world's most devastating crop diseases. One of the reasons they are such successful pathogens is because several fungi have evolved the capacity to breach the tough outer cuticle of plants using specialized infection structures called appressoria. This is exemplified by the filamentous ascomycete fungus Magnaporthe oryzae, causal agent of rice blast, one of the most serious diseases affecting rice cultivation globally.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!