Iron in airway macrophages and infective exacerbations of chronic obstructive pulmonary disease

Background Excess pulmonary iron has been implicated in the pathogenesis of lung disease, including asthma and COPD. An association between higher iron content in sputum macrophages and infective exacerbations of COPD has previously been demonstrated. Objectives To assess the mechanisms of pulmonary macrophage iron sequestration, test the effect of macrophage iron-loading on cellular immune function, and prospectively determine if sputum hemosiderin index can predict infectious exacerbations of COPD. Methods Intra- and extracellular iron was measured in cell-line-derived and in freshly isolated sputum macrophages under various experimental conditions including treatment with exogenous IL-6 and hepcidin. Bacterial uptake and killing were compared in the presence or absence of iron-loading. A prospective cohort of COPD patients with defined sputum hemosiderin indices were monitored to determine the annual rate of severe infectious exacerbations. Results Gene expression studies suggest that airway macrophages have the requisite apparatus of the hepcidin-ferroportin axis. IL-6 and hepcidin play roles in pulmonary iron sequestration, though IL-6 appears to exert its effect via a hepcidin-independent mechanism. Iron-loaded macrophages had reduced uptake of COPD-relevant organisms and were associated with higher growth rates. Infectious exacerbations were predicted by sputum hemosiderin index (β = 0.035, p = 0.035). Conclusions We demonstrate in-vitro and population-level evidence that excess iron in pulmonary macrophages may contribute to recurrent airway infection in COPD. Specifically, IL-6-dependent iron sequestration by sputum macrophages may result in immune cell dysfunction and ultimately lead to increased frequency of infective exacerbation.

Copper selects for siderophore-mediated virulence in Pseudomonas aeruginosa

Iron is essential for almost all bacterial pathogens and consequently it is actively withheld by their hosts. The production of extracellular siderophores however enables iron sequestration by pathogens, increasing their virulence. Another function of siderophores is extracellular detoxification of non-ferrous metals. Here, we experimentally link the detoxification and virulence roles of siderophores by testing whether the opportunistic pathogen Pseudomonas aeruginosa displays greater virulence after exposure to copper stress. We incubated P. aeruginosa under different copper regimes for either two or twelve days. Subsequent growth in a copper-free environment removed phenotypic effects, before quantification of pyoverdine production (P. aeruginosa’s primary siderophore) and virulence using the Galleria mellonella infection model. Copper selected for increased pyoverdine production, which was positively associated with virulence. This effect increased with time. We here show a direct link between metal stress and bacterial virulence, highlighting another dimension of the detrimental effects of metal pollution on human health.

Development of Iron Sequester Antioxidant Quercetin@ZnO Nanoparticles with Photoprotective Effects on UVA-Irradiated HaCaT Cells

Background. Solar ultraviolet radiation A (UVA, 320-400 nm) is a significant risk factor leading to various human skin conditions such as premature aging or photoaging. This condition is enhanced by UVA-mediated iron release from cellular iron proteins affecting huge populations across the globe. Purpose. Quercetin-loaded zinc oxide nanoparticles (quercetin@ZnO NPs) were prepared to examine its cellular iron sequestration ability to prevent the production of reactive oxygen species (ROS) and inflammatory responses in HaCaT cells. Methods. Quercetin@ZnO NPs were synthesized through a homogenous precipitation method, and the functional groups were characterized by Fourier transform infrared (FTIR) spectroscopy, whereas scanning electron microscopy (SEM) described the morphologies of NPs. MTT and qRT-PCR assays were used to examine cell viability and the expression levels of various inflammatory cytokines. The cyclic voltammetry (CV) was employed to evaluate the redox potential of quercetin-Fe3+/quercetin-Fe2+ complexes. Results. The material characterization results supported the loading of quercetin molecules on ZnO NPs. The CV and redox potential assays gave Fe-binding capability of quercetin at 0.15 mM and 0.3 mM of Fe(NO3)3. Cytotoxicity assays using quercetin@ZnO NPs with human HaCaT cells showed no cytotoxic effects and help regain cell viability loss following UVA (150 kJ/m2). Conclusion. Quercetin@ZnO NPs showed that efficient quercetin release action is UV-controlled, and the released quercetin molecules have excellent antioxidant, anti-inflammatory, and iron sequestration potential. Quercetin@ZnO NPs have superior biocompatibility to provide UVA protection and medication at once for antiphotoaging therapeutics.

Mucormycosis its Pathogenesis and Treatment

Mucormycosis is an ailment that originates from a saprophyte. Mucorales are a group of a growing number of members who have mucormycosis. The environmental contamination with fungal spore and now in COVID-19 the high use of steroid, which increases the occasion of mucor. It is a worldwide infectious disease as well as there is no vaccine to treat mucormycosis. Therapies for mucormycosis involve a coordinated surgical and medical approach. Antifungal therapy, iron sequestration, and adjunctive therapy are the various therapies to treat mucormycosis that will discuss in the article. Also the pathogenesis, identification of mucormycosis will review here.

Draft Genome Sequences of Pseudomonas spp. Isolated from Berry Surfaces in Commercial Cranberry Bogs in Massachusetts, USA

The surfaces of plants are colonized by a rich diversity of microbes but are largely unexplored. Here, we present the draft genome sequences of five Pseudomonas spp. isolated from cultivated cranberry fruit surfaces. Although the isolates represent four different species, their genomes all contain conserved iron-sequestration and uptake genes.

Disruption of the surfactant protein A receptor SP-R210L (CD245α/MYO18Aα) alters respiratory function and iron sequestration in alveolar macrophages of aged mice

Previous studies demonstrated that the host defense collectins, surfactant protein A and complement component 1q, modulate tissue-dependent macrophage activation, pathogen clearance, and regulatory macrophage functions through the receptor SP-R210, which consists of two isoforms SP-R210L and SP-R210S. These isoforms are encoded by alternatively spliced mRNAs of the Myo18A gene. The present study in conditional transgenic mice revealed novel age-related functions of the SP-R210L isoform in modulating pulmonary mechanics, iron sequestration in alveolar macrophages, and life-long maintenance of the alveolar macrophage population. Our findings support the novel idea that SP-R210L-deficient AMs undergo bi-directional epigenetic adaptation that results in chronic dysregulation of broncho-alveolar function, immune homeostasis, and maintenance of oncotic balance at the airway-capillary interface. Disruption of SP-R210L increases the risk for development of severe interstitial lung disease during development and aging.

TOR functions as a molecular switch connecting an iron cue with host innate defense against bacterial infection

As both host and pathogen require iron for survival, iron is an important regulator of host-pathogen interactions. However, the molecular mechanism by which how the availability of iron modulates host innate immunity against bacterial infections remains largely unknown. Using the metazoan Caenorhabditis elegans as a model, we demonstrate that infection with a pathogenic bacterium Salmonella enterica serovar Typhimurium induces autophagy by inactivating the target of rapamycin (TOR). Although the transcripts of ftn-1 and ftn-2 encoding two H-ferritin subunits are upregulated upon S. Typhimurium infection, the ferritin protein is kept at a low level due to its degradation mediated by autophagy. Autophagy, but not ferritin, is required for defense against S. Typhimurium infection under normal circumstances. Increased abundance of iron suppresses autophagy by activating TOR, leading to an increase in the ferritin protein level. Iron sequestration, but not autophagy, becomes pivotal to protect the host from S. Typhimurium infection in the presence of exogenous iron. Our results show that TOR acts as a regulator linking iron availability with host defense against bacterial infection.

Transferrin-mediated iron sequestration suggests a novel therapeutic strategy for controlling Nosema disease in the honey bee, Apis mellifera

Nosemosis C, a Nosema disease caused by microsporidia parasite Nosema ceranae, is a significant disease burden of the European honey bee Apis mellifera which is one of the most economically important insect pollinators. Nevertheless, there is no effective treatment currently available for Nosema disease and the disease mechanisms underlying the pathological effects of N. ceranae infection in honey bees are poorly understood. Iron is an essential nutrient for growth and survival of hosts and pathogens alike. The iron tug-of-war between host and pathogen is a central battlefield at the host-pathogen interface which determines the outcome of an infection, however, has not been explored in honey bees. To fill the gap, we conducted a study to investigate the impact of N. ceranae infection on iron homeostasis in honey bees. The expression of transferrin, an iron binding and transporting protein that is one of the key players of iron homeostasis, in response to N. ceranae infection was analysed. Furthermore, the functional roles of transferrin in iron homeostasis and honey bee host immunity were characterized using an RNA interference (RNAi)-based method. The results showed that N. ceranae infection causes iron deficiency and upregulation of the A. mellifera transferrin (AmTsf) mRNA in honey bees, implying that higher expression of AmTsf allows N. ceranae to scavenge more iron from the host for its proliferation and survival. The suppressed expression levels of AmTsf via RNAi could lead to reduced N. ceranae transcription activity, alleviated iron loss, enhanced immunity, and improved survival of the infected bees. The intriguing multifunctionality of transferrin illustrated in this study is a significant contribution to the existing body of literature concerning iron homeostasis in insects. The uncovered functional role of transferrin on iron homeostasis, pathogen growth and honey bee’s ability to mount immune responses may hold the key for the development of novel strategies to treat or prevent diseases in honey bees.