Biology subjects

Castiglione, K.

Publications and source records attributed to Castiglione, K..

5 recordsLinked to original sources

bioRxiv2026

Mixtures that Matter: Correlation Patterns in Antibacterial and Cytotoxic Activities of Five Hop Isolates

Antimicrobial resistance (AMR) has resulted in the need for the development of alternative strategies for combating pathogens and growth promotion of poultry, including the use of plant-derived compounds such as hop (Humulus lupulus) isolates. The present study evaluates the correlation patterns of the biological activity of five major hop isolates (humulone, lupulone, isohumulone, xanthohumol, and isoxanthohumol) against Bacillus subtilis, Micrococcus luteus, and a chicken cell line UMNSAH/DF-1 using a two-dimensional checkerboard assay. Fractional inhibitory concentrations ({sum}FIC) were used to classify interactions as additive, synergistic, or antagonistic, and selectivity indices assessed antibacterial versus cytotoxic effects. On B. subtilis, combinations were predominantly additive, whereas M. luteus, in contrast, showed variable interactions, including also synergistic (humulone + lupulone) and antagonistic combinations (isohumulone + isoxanthohumol), demonstrating the impact of the metabolic resilience of the target organism. Cytotoxicity in UMNSAH/DF-1 cells was largely additive, with synergistic effects observed only for isomerized compounds. Selectivity analysis highlighted humulone-lupulone combinations as most favorable, offering high antibacterial activity with minimal cytotoxicity. These results provide novel insights for selecting hop isolate combinations for the development of phytogenic feed additives (PFAs), emphasizing that both compound composition and target organism physiology critically shape efficacy and safety outcomes.

microbiology↗

bioRxiv2025

Il33 expressing cDC2s promote expansion of ILC2s and eosinophilia in fungal airway inflammation in male mice

Eosinophilic allergic asthma is often associated with fungal sensitization and represents the dominant form of asthma in adolescents. The mechanisms by which lung eosinophilia is regulated in this context are incompletely understood. Here, we demonstrate that type 2 innate lymphoid cells (ILC2s) are generally required in addition to Th2 cells for Aspergillus fumigatus-elicited eosinophilic lung inflammation in mice and this effect was independent of ILC2-derived IL-5. Surprisingly, expansion of ILC2s in male mice was ST2-independent, but required expression of Il33 in cDC2s induced by Th2-derived IL-4/13. This IL-33-plus IL-4-regulated transcriptional module in cDC2s included expression of factors associated with activation of ILC2s and was restricted to CCR7+ cDC2s in the inflamed lung. Our findings uncovered a novel intimate cross-talk between IL-33+ cDC2s, ILC2s and Th2 cells to orchestrate eosinophilia in a sex-dependent manner upon A. fumigatus-induced allergic lung inflammation.

immunology↗

bioRxiv2022

Quantitative proteomics and lipidomics of TFG-deficient B cells provide insights into mechanisms of autophagic flux and plasma cell biology

The autophagy-flux-promoting protein TFG (Trk-fused gene) is up-regulated during B cell differentiation into plasma cells and supports survival of CH12 B cells. We hypothesized that quantitative proteomics analysis of CH12tfgKO B cells with intact or blocked autophagy-lysosome flux (via NH4Cl) will identify mechanisms of TFG-dependent autophagy, plasma cell biology and B cell survival. Analysis of CH12WT B cells in the presence of NH4Cl will identify proteins whose presence is continuously regulated by lysosomes independent of TFG. We determined hundreds of proteins to be controlled by TFG and/or NH4Cl. Notably, NH4Cl treatment alone increased the abundance of a cluster of cytosolic and mitochondrial translational proteins while it also reduced a number of proteins. Within the B cell relevant protein pool, BCL10 was reduced, while JCHAIN was increased in CH12tfgKO B cells. Furthermore, TFG regulated the abundance of transcription factors, such as JUNB, metabolic enzymes, such as the short-chain fatty acid activating enzyme ACOT9 or the glycolytic enzyme ALDOC. Gene ontology enrichment analysis revealed that TFG-regulated proteins localized to mitochondria and membrane-bounded organelles. Due to these findings we performed shotgun lipidomics of glycerophospholipids, uncovering that a particular phosphatidylethanolamine (PE) species, 32:0 PE, which lipidates LC3 most efficiently, was less abundant while phosphatidylglycerol (PG) was more abundant in CH12tfgKO B cells. In line with the role of PG as precursor for Cardiolipin (CL), the CL content was higher in CH12tfgKO B cells and addition of PG liposomes to B cells increased the amount of CL. We propose a role for TFG in B cell activation and plasma cell biology via regulation of proteins involved in germinal center and plasma cell development, such as BCL10 or JCHAIN, as well as in lipid homeostasis, mitochondria and metabolism.

immunology↗

bioRxiv2021

Inhibitory properties of microalgal extracts on the in vitro replication of cyprinid herpesvirus 3

Microalgae often stand out for their high biodiversity as well as their associated large number of potent bioactives. Therefore, they are interesting candidates as possible sources of antiviral substances, e.g. against cyprinid herpesvirus 3 (CyHV-3). Although this virus leads to high mortalities in aquacultures, there is no treatment available yet. Hence, ethanolic extracts produced with accelerated solvent extraction from six microalgal species (Arthrospira platensis, Chlamydomonas reinhardtii, Chlorella kessleri, Haematococcus pluvialis, Nostoc punctiforme and Scenedesmus obliquus) were examined in this study for inhibitory effects on viral replication. An inhibition of the in vitro replication of CyHV-3 in common carp brain cells could be confirmed for all six species, with the greatest effect for the C. reinhardtii and H. pluvialis extracts. At still non-cytotoxic concentrations viral DNA replication was reduced by over 3 orders of magnitude (> 99.9 %) each compared to the untreated replication controls, while the virus titers were at or even below the limit of detection. When pre-incubating cells and virus with C. reinhardtii and especially H. pluvialis extracts before inoculation, the reduction of viral DNA and virus titer was even stronger. Based on these results, an intervention in the initial replication steps like viral adsorption or membrane fusion is assumed. Moreover, a protection mechanism preventing the production of viral proteins and the assembly of mature virions is also possible. All in all, the results show that microalgae are a very promising source of natural antiviral substances against CyHV-3.

bioengineering↗

bioRxiv2021

Mitochondrial function is essential for humoral immunity by controlling flux of the TCA cycle, phosphatidic acid and mTOR activity in B cells

The function of mitochondrial respiration during B cell fate decisions and differentiation remains equivocal. This study reveals that selection for mitochondrial fitness occurs during B cell activation and is essential for subsequent plasma cell differentiation. By expressing a mutated mitochondrial helicase in transitional B cells, we depleted mitochondrial DNA during B cell maturation, resulting in reduced oxidative phosphorylation. Although no changes in follicular B cell development were evident, germinal centers, class switch recombination to IgG, plasma cell generation and humoral immunity were diminished. Defective oxidative phosphorylation led to aberrant flux of the tricarboxylic acid cycle and lowered the amount of saturated phosphatidic acid. Consequently, MTOR activity and BLIMP-1 induction were curtailed whereas HIF1, glycolysis and AMPK activity were amplified. Exogenous phosphatidic acid increased mTOR activity in activated B cells. Hence, mitochondrial function is required and selected for in activated B cells for the successful generation of functional plasma cells.

immunology↗