Immunity to Invasive Fungal Diseases

Invasive fungal diseases are rare in individuals with intact immunity. This, together with the fact that there are only a few species that account for most mycotic diseases, implies a remarkable natural resistance to pathogenic fungi. Mammalian immunity to fungi rests on two pillars, powerful immune mechanisms and elevated temperatures that create a thermal restriction zone for most fungal species. Conditions associated with increased susceptibility generally reflect major disturbances of immune function involving both the cellular and humoral innate and adaptive arms, which implies considerable redundancy in host defense mechanisms against fungi. In general, tissue fungal invasion is controlled through either neutrophil or granulomatous inflammation, depending on the fungal species. Neutrophils are critical against Candida spp. and Aspergillus spp. while macrophages are essential for controlling mycoses due to Cryptococcus spp., Histoplasma spp., and other fungi. The increasing number of immunocompromised patients together with climate change could significantly increase the prevalence of fungal diseases. Expected final online publication date for the Annual Review of Immunology, Volume 40 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The Vacuolar Transporter OsNRAMP2 Mediates Fe Remobilization During Germination and Affects Cd Distribution to Rice Grain

Background and aims Iron (Fe) deficiency in plants is a common problem affecting agricultural production. Cadmium (Cd) is a toxic metal that can be taken up and transported within plants by transporters for divalent metals including Fe(II). The present study aims to investigate the functions of OsNRAMP2 (Natural Resistance-Associated Macrophage Protein 2) in the remobilization and distribution of Fe and Cd in rice. Methods The expression pattern of OsNRAMP2 was determined by quantitative real-time PCR and pOsNRAMP2:GUS assay. Knockout mutants of OsNRAMP2 were generated by using CRISPR/Cas9 gene editing. Localization of Fe in the vacuolar globoids of germinating seeds was imaged by high-resolution transmission electron microscopy coupled with energy-dispersive X-ray spectroscopy. Distributions of Fe and Cd between different plant tissues were investigated in hydroponic and soil pot experiments. Results OsNRAMP2 was mainly expressed in the embryo of germinating seeds, roots, leaf sheaths and leaf blades. OsNRAMP2 was localized at the tonoplast. Knockout of OsNRAMP2 delayed seed germination and produced chlorotic seedling leaves. Remobilization of Fe stored in the protein storage vacuoles in the scutellum of germinating seeds was restricted in osnramp2 mutants compared with wild type. Expression of genes related to Fe uptake was enhanced in the seedlings of osnramp2 mutants. Knockout of OsNRAMP2 significantly decreased the distribution of Cd, but not Fe, from leaves and straws to rice grains. Conclusions OsNRAMP2 plays an important role in remobilizing vacuolar Fe during seed germination and affects translocation of Cd from vegetative tissues to rice grains.

Microbial source tracking and antimicrobial resistance in one river system of a rural community in Bahia, Brazil

Use of antibiotics inevitably leads to antimicrobial resistance. Selection for resistance occurs primarily within the gut of humans and animals as well as in the environment through natural resistance and residual antibiotics in streams and soil. We evaluated antimicrobial resistance in Gram negative bacteria from a river system in a rural community in Bahia, Brazil. Water was collected from the Jiquiriçá and Brejões rivers and the piped water supply. Additionally, stools were collected from a random sample of residents, cows, pigs and horses near the river. The samples were screened for bacteria resistant to ciprofloxacin, cefotaxime, and meropenem and identified biochemically at the genus and species levels. Microbial source tracking demonstrated that ruminant and human fecal contamination increased as the rivers neared the village center and decreased after the last residence. Antibiotic bacteria were identified from all samples (n = 32). No bacteria were resistant to carbapenems, but the majority of the enterobacteria were resistant to ciprofloxacin, even though this class of antibiotics is not commonly used in food animals in this region. Considering these facts, together with the pattern of human fecal contamination, a human source was considered most likely for these resistant isolates.

Potential of germanium-based compounds in coronavirus infection

The first germanium compounds which exhibited immunomodulatory and antiviral effects were sesquioxane-type germanates. To date, more than a dozen compounds containing germanium have been synthesized and are being actively studied. They include germanium carboxylates and citrates, complexes of germanium with resveratrol, daphnetin, mangiferin, chrysin, quercetin, ascorbic and nicotinic acids, amino acids, gamma-lactones, germanium-containing spirulina, yeast and others. Germanium-based compounds have shown the ability to influence the replication of various DNA/RNA viruses, stimulate the body’s natural resistance, prevent the development of metabolic intoxication of various origin, increase the efficacy of vaccines, and prevent the development of excessive accumulation of reactive oxygen species, which plays a decisive role in the development of inflammatory response caused by a viral infection. It seems reasonable to say that germanium-based complex compounds effectively contribute to the preservation of high--energy bonds in the form of ATP, optimize the activity of metabolic processes by re-oxygenation, and exhibit antimicrobial activity. The purpose of this review is to summarize the pharmacological potential of various germanium-based compounds studied nowadays, taking into account their mechanisms of action, and to analyze their prospects in the development of integrated approaches in the prevention and treatment of SARS-CoV-2 infection.

Salicylic acid effect on the mechanism of Lelliottia amnigena causing potato soft rot

Salicylic acid (SA) plays an important role in protecting plants from biotic stresses. Lelliottia amnigena is a newly identified potato soft rot pathogen and there are no adequate studies on this soft rot pathogen. Therefore, this paper focussed on the effect of SA on the mechanism under which L. amnigena causes potato soft rot. L. amnigena was examined and detected to secrete pectinase, proteases, pectin lyase and cellulase, which are the most important pathogenic enzymes involved in the production of plant diseases. Sterilised healthy potato tubers were inoculated with 0.2 mL of L. amnigena suspension (3.69 CFU · mL−1 × 107 CFU · mL−1). After 24 h, 200 μL of four different SA concentrations (0.5 mM, 1.0 mM, 1.5 mM and 2.0 mM) were used to treat the tubers. Co-culture of L. amnigena and SA significantly reduced the activity of pectinase, protease, pectin lyase and cellulase by an average of 33.8%, 43.4%, 67.7% and 46.9%, across the four concentrations (0.5 mM, 1.0 mM, 1.5 mM and 2.0 mM), respectively, compared to the control. The average disease index was reduced by 54.7% across the four SA concentrations. Treatment with SA induced transcriptional levels of the superoxide dismutase, peroxide, catalase and glutathione S-transferase across the four levels by an average of 3.87, 3.25, 3.97 and 3.94-fold, respectively, compared to control. Based on our results, we could state that SA could reduce the activities of these extracellular enzymes produced by L. amnigena by modulating both enzymatic and non-enzymatic antioxidant activities and gene expression that induce natural resistance in plants against bacterial infections.

The effectiveness of mineral adaptogen in experimental immunosuppression

Modern conditions of animal husbandry and poultry farming dictate a continuous search for effective means that increase the natural resistance of the organism of farm animals and poultry. The purpose of the study. In this regard, an experimental study was conducted on laboratory animals using a mineral adaptogen of domestic production in order to determine its effectiveness in conditions of artificially induced immunosuppression. The objectives of the study were to determine the immunobiochemical status, subcellular and intra-organ changes in the organs of the immune system at all levels. Research methods. Experimental studies were carried out using generally accepted zootechnical, pathomorphological, histological, immunobiochemical and statistical research methods. Results. Immunobiochemical changes in the body of experimental animals are described. Microscopic changes at the level of tissues and cells in the organs of the immune system at all levels are described. Changes in the organs of the immune system during immunosuppression and against the background of feeding mineral adaptogen are described. Morphological examination of the immune system organs in experimental animals revealed prolonged immunosuppressive changes for 14 days. At the same time, after induced immunosuppression, significant structural changes remain in the central and peripheral organs of the immune system in the form of lymphoid tissue atrophy (in the thymus, both in the organ of central immunogenesis and in the organs of the peripheral immune system – the spleen and lymph nodes and intra-organ lymph formations). During histological studies, the structure of cells and tissues, when using a mineral adaptogen, was more morphologically mature and was in a functionally active state, and dystrophic and necrotic processes were observed in the control group. The conducted studies convincingly prove the effect of mineral adaptogen on increasing natural resistance and its immunoprotective properties. Scientific novelty. For the first time in experimental conditions, a simultaneous assessment of the immunobiochemical parameters of the blood of laboratory animals and a microscopic examination of the organs of the immune system at all levels with morphometric analysis of the data obtained were given. As a result of the conducted studies, the immuno- and organoprotective effect of feeding the mineral adaptogen was proved and the immunomodulatory effect was morphometrically confirmed.

Nematode RALF-Like 1 Targets Soybean Malectin-Like Receptor Kinase to Facilitate Parasitism

Soybean [Glycine max (L.) Merr. ] is one of the most strategical oilseed crops that provides sustainable source of protein and oil worldwide. Cultivation of soybean is severely affected by root-knot nematode (RKN). However, the mechanism of RKN parasitism to soybeans is largely unknown. In this study, we identify GmLMM1, which encodes a homolog of FERONIA-like receptor kinase in soybean, as a susceptible gene toward nematode. Mutations of GmLMM1 exhibit enhanced resistance against the RKN Meloidogyne incognita. RNA-sequencing (RNA-seq) analysis reveals a similar differential expression pattern for genes regulated by GmLMM1 (Gmlmm1 vs. wild-type) and M. incognita (M. incognita vs. mock), supporting the role of GmLMM1 in M. incognita infection. Unlike FERONIA in Arabidopsis, GmLMM1 specifically binds to MiRALF1 and AtRALF23 that suppress plant immunity, but not MiRALF3 and AtRALF1. Moreover, we found that the single-nucleotide polymorphism (SNP) in GmLMM1 leads to the natural resistance against RKNs in soybeans. Collectively, these findings uncover GmLMM1 as a susceptible target of nematode RALF-like 1 and provide new genetic resource for nematode resistant breeding.

Manganese is a Physiologically Relevant TORC1 Activator in Yeast and Mammals.

The essential biometal manganese (Mn) functions as a cofactor for several enzymatic activities that are critical for the prevention of human diseases. Whether intracellular Mn levels may also modulate signaling events has so far remained largely unexplored. The target of rapamycin complex 1 (TORC1, mTORC1 in mammals) is a conserved protein kinase complex that requires metal co-factors to phosphorylate its downstream effectors as part of a central, homeostatic process that coordinates cell growth and metabolism in response to nutrient and/or growth factor availability. Using genetic and biochemical approaches, we show here that TORC1 activity is exquisitely sensitive to stimulation by Mn both in vivo and in vitro. Mn-mediated control of TORC1 depends on Smf1 and Smf2, two members of the family of natural resistance-associated macrophage protein (NRAMP) metal ion transporters, the turnover of which is subjected to feedback control by TORC1 activity. Notably, increased Mn levels and consequent activation of TORC1 cause retrograde dysregulation and antagonize the rapamycin-induced gene expression and autophagy programs in yeast. Because Mn also activates mTORC1 signaling in aminoacid starved human cells, our data indicate that intracellular Mn levels may constitute an evolutionary conserved physiological cue that modulates eukaryotic TORC1/mTORC1 signaling. Our findings therefore reveal a hitherto elusive connection between intracellular Mn levels, mTORC1 activity, and human diseases.