Iron at the interface of immunity and infection DOI Creative Commons
Manfred Nairz, David Haschka, Egon Demetz

et al.

Frontiers in Pharmacology, Journal Year: 2014, Volume and Issue: 5

Published: July 16, 2014

Both, mammalian cells and microbes have an essential need for iron, which is required many metabolic processes microbial pathogenicity. In addition, cross-regulatory interactions between iron homeostasis immune function are evident. Cytokines the acute phase protein hepcidin affect leading to retention of metal within macrophages hypoferremia. This considered result from a defense mechanism body limit availability extracellular pathogens while on other hand reduction circulating results in development anemia inflammation. Opposite, erythropoiesis inducing hormone erythropoietin innate responses by influencing interferon-gamma (IFN-γ) mediated (iron) or NF-kB inducible (erythropoietin) effector pathways macrophages. Thus, loaded with lose their ability kill intracellular via IFN-γ such as nitric oxide (NO) formation. Accordingly, invaded bacterium Salmonella enterica serovar Typhimurium increase expression export ferroportin thereby reducing intramacrophage bacteria side strengthening anti-microbial macrophage increased formation NO TNF-α. certain resistance genes natural associated (Nramp1) lipocalin-2 exert part antimicrobial activity controlling host and/or homeostasis. Consequently, pharmacological dietary modification cellular trafficking enhances but may susceptibility compartment vice versa. control over central battlefield host-pathogen interplay course infectious disease favor either pathogenic invader.

Language: Английский

Candida albicanspathogenicity mechanisms DOI Open Access
François L. Mayer, Duncan Wilson, Bernhard Hube

et al.

Virulence, Journal Year: 2013, Volume and Issue: 4(2), P. 119 - 128

Published: Feb. 7, 2013

The polymorphic fungus Candida albicans is a member of the normal human microbiome. In most individuals, C. resides as lifelong, harmless commensal. Under certain circumstances, however, can cause infections that range from superficial skin to life-threatening systemic infections. Several factors and activities have been identified which contribute pathogenic potential this fungus. Among them are molecules mediate adhesion invasion into host cells, secretion hydrolases, yeast-to-hypha transition, contact sensing thigmotropism, biofilm formation, phenotypic switching fitness attributes. Our understanding when how these mechanisms infection has significantly increased during last years. addition, novel virulence recently discovered. review we present an update on our current pathogenicity important pathogen.

Language: Английский

Citations

1641
The Physiological, Biochemical, and Molecular Roles of Zinc Transporters in Zinc Homeostasis and Metabolism DOI
Taiho Kambe,

Tokuji Tsuji,

Ayako Hashimoto

et al.

Physiological Reviews, Journal Year: 2015, Volume and Issue: 95(3), P. 749 - 784

Published: June 18, 2015

Zinc is involved in a variety of biological processes, as structural, catalytic, and intracellular intercellular signaling component. Thus zinc homeostasis tightly controlled at the whole body, tissue, cellular, subcellular levels by number proteins, with transporters being particularly important. In metazoan, two transporter families, Zn (ZnT) Zrt-, Irt-related proteins (ZIP) function mobilization influx, efflux, compartmentalization/sequestration across membranes. During last decades, significant progress has been made understanding molecular properties, expression, regulation, cellular physiological roles ZnT ZIP transporters, which underpin multifarious functions zinc. Moreover, growing evidence indicates that malfunctioning due to dysfunction results onset progression diseases. This review summarizes current our each from perspective physiology pathogenesis, discussing challenging issues their structure transport mechanisms.

Language: Английский

Citations

934
Aspergillus fumigatus and Aspergillosis in 2019 DOI Open Access
Jean‐Paul Latgé, Georgios Chamilos

Clinical Microbiology Reviews, Journal Year: 2019, Volume and Issue: 33(1)

Published: Nov. 12, 2019

Aspergillus fumigatus is a saprotrophic fungus; its primary habitat the soil. In ecological niche, fungus has learned how to adapt and proliferate in hostile environments. This capacity helped resist survive against human host defenses and, further, be responsible for one of most devastating lung infections terms morbidity mortality.

Language: Английский

Citations

864
Macrophage defense mechanisms against intracellular bacteria DOI Creative Commons
Günter Weiß, Ulrich E. Schaible

Immunological Reviews, Journal Year: 2015, Volume and Issue: 264(1), P. 182 - 203

Published: Feb. 20, 2015

Summary Macrophages and neutrophils play a decisive role in host responses to intracellular bacteria including the agent of tuberculosis ( TB ), M ycobacterium as they represent forefront innate immune defense against bacterial invaders. At same time, these phagocytes are also primary targets be abused cells. Their efficacy contain eliminate . decides whether patient initially becomes infected or not. However, when infection chronic even latent (as case ) despite development specific activation, have important effector functions. evolved myriad strategies combat with such These include induction toxic anti‐microbial effectors nitric oxide reactive oxygen intermediates, stimulation microbe intoxication mechanisms via acidification metal accumulation phagolysosome, restriction microbe's access essential nutrients iron, fatty acids, amino production peptides cytokines, along autophagy efferocytosis pathogen. On other hand, , prime example well‐adapted facultative bacterium, has learned during evolution counter‐balance host's secure survival multiplication within this otherwise hostile environment. This review provides an overview macrophages directed focus on Gaining more insights knowledge into complex network host‐pathogen interaction will identify novel target sites intervention successfully clear at time rapidly emerging multi‐resistance conventional antibiotics.

Language: Английский

Citations

845
The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages DOI Creative Commons

Julie Schulthess,

Sumeet Pandey,

Melania Capitani

et al.

Immunity, Journal Year: 2019, Volume and Issue: 50(2), P. 432 - 445.e7

Published: Jan. 25, 2019

Language: Английский

Citations

793
Iron homeostasis and oxidative stress: An intimate relationship DOI Creative Commons

Dimitrios Galaris,

Alexandra Barbouti, Kostas Pantopoulos

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2019, Volume and Issue: 1866(12), P. 118535 - 118535

Published: Aug. 22, 2019

Language: Английский

Citations

661
Metal homeostasis and resistance in bacteria DOI
Pete Chandrangsu, Christopher Rensing, John D. Helmann

et al.

Nature Reviews Microbiology, Journal Year: 2017, Volume and Issue: 15(6), P. 338 - 350

Published: March 27, 2017

Language: Английский

Citations

632
Manganese Increases the Sensitivity of the cGAS-STING Pathway for Double-Stranded DNA and Is Required for the Host Defense against DNA Viruses DOI Creative Commons
Chenguang Wang, Yukun Guan,

Mengze Lv

et al.

Immunity, Journal Year: 2018, Volume and Issue: 48(4), P. 675 - 687.e7

Published: April 1, 2018

Language: Английский

Citations

575
Resolution of Inflammation: What Controls Its Onset? DOI Creative Commons
Michelle A. Sugimoto, Lirlândia P. Sousa, Vanessa Pinho

et al.

Frontiers in Immunology, Journal Year: 2016, Volume and Issue: 7

Published: April 26, 2016

An effective resolution program may be able to prevent the progression from non-resolving acute inflammation persistent chronic inflammation. It has now become evident that coordinated programs initiate shortly after inflammatory responses begin. In this context, several mechanisms provide fine-tuning of and create a favorable environment for phase take place homeostasis return. review, we focus on events required an transition proinflammatory onset establishment resolution. We suggest mediators promote can simultaneously active Indeed, enact decrease in local chemokine concentration, reduction which is essential inhibit further infiltration neutrophils into tissue. Interestingly, although are cells characteristically participate inflammation, they also contribute Further understanding molecular instrumental develop pro-resolution strategies treat complex diseases humans. The efforts based have shaped new area pharmacology referred as 'resolution pharmacology'.

Language: Английский

Citations

552
Iron metabolism and iron disorders revisited in the hepcidin era DOI Creative Commons
Clara Camaschella, Antonella Nai, Laura Silvestri

et al.

Haematologica, Journal Year: 2020, Volume and Issue: 105(2), P. 260 - 272

Published: Jan. 16, 2020

Iron is biologically essential, but also potentially toxic; as such it tightly controlled at cell and systemic levels to prevent both deficiency overload. regulatory proteins post-transcriptionally control genes encoding that modulate iron uptake, recycling storage are themselves regulated by iron. The master regulator of homeostasis the liver peptide hepcidin, which controls serum through degradation ferroportin in iron-absorptive enterocytes iron-recycling macrophages. This review emphasizes most recent findings biology, deregulation hepcidin-ferroportin axis disorders how research results have an impact on clinical disorders. Insufficient hepcidin production central overload while excess leads restriction. Mutations hemochro-matosis result downregulating BMP-SMAD signaling pathway or causing hepcidin-resistance. In iron-loading anemias, β-thalassemia, enhanced albeit ineffective ery-thropoiesis releases erythroferrone, sequesters BMP receptor ligands, thereby inhibiting hepcidin. iron-refractory, iron-deficiency ane-mia mutations inhibitor TMPRSS6 upregulate pathway. Interleukin-6 acute chronic inflammation increases levels, iron-restricted erythropoiesis presence iron-replete Our improved understanding its regulation having established schedules oral treatment choice versus intravenous management deficiency. Moreover leading development targeted therapies for inflammation, mainly centered manipulation axis.

Language: Английский

Citations

518