Antimicrobial activity of skin secretions isolated from Indian toad, Bufo melanostictus Schneider 1799

Amphibians like toads have been known to secrete antimicrobial secretions outside their body into their environments, through skin pores and parotid glands. Toad skin-secretions contain four types of compounds namely, biogenic amines, bufadienolides, alkaloids & steroids and peptides & proteins. Bulk of research relating to amphibian antimicrobial secretions has been done on frogs. In toads, such research has only been done in South America, Europe and China. Antimicrobial secretions vary considerably from specie-to-specie and drastically across various biomes. This prompted us to examine and confirm presence of antimicrobial activity (if any) in Indian Common Toad (Bufo melanostictus Schneider 1799) skin secretions since; no such analysis had been previously done on this toad which is found all across the South-east Asia. The antibacterial potency of toad skin secretions was tested against the bacteria, Escherichia coli. After running preliminary antibacterial analysis assays, we found that these cutaneous secretions retrieved from Indian Common Toad possessed potential bactericidal activity. The results that we got confirmed that some unexplored bactericidal components were present in skin secretions of these toads. These conclusions call for further research into biochemistry and molecular characterization of these components

Immature, Semi-mature and Fully mature Dendritic Cells: Towards a DC-cancer cells interface that augments anticancer immunity

Dendritic cells (DCs) are the sentinel antigen-presenting cells of the immune system; such that their productive interface with the dying cancer cells is crucial for proper communication of the non-self status of cancer cells to the adaptive immune system. Efficiency and the ultimate success of such a communication hinges upon the maturation status of the DCs, attained following their interaction with cancer cells. Immature DCs facilitate tolerance towards cancer cells (observed for many apoptotic inducers) while fully mature DCs can strongly promote anticancer immunity if they secrete the correct combinations of cytokines (observed when DCs interact with cancer cells undergoing immunogenic cell death (ICD)). However, an intermediate population of DC maturation, called semi-mature DCs exists, which can potentiate either tolerogenicity or pro-tumourigenic responses (as happens in the case of certain chemotherapeutics and agents exerting ambivalent immune reactions). Specific combinations of DC phenotypic markers, DC-derived cytokines/chemokines, dying cancer cell-derived danger signals and other less characterized entities (e.g. exosomes) can define the nature and evolution of the DC maturation state. In the present review, we discuss these different maturation states of DCs, how they might be attained and which anticancer agents or cell death modalities (e.g. tolerogenic cell death vs. ICD) may regulate these states

Discriminating mild from critical COVID-19 by innate and adaptive immune single-cell profiling of bronchoalveolar lavages.

How the innate and adaptive host immune system miscommunicate to worsen COVID-19 immunopathology has not been fully elucidated. Here, we perform single-cell deep-immune profiling of bronchoalveolar lavage (BAL) samples from 5 patients with mild and 26 with critical COVID-19 in comparison to BALs from non-COVID-19 pneumonia and normal lung. We use pseudotime inference to build T-cell and monocyte-to-macrophage trajectories and model gene expression changes along them. In mild COVID-19, CD8+ resident-memory (TRM) and CD4+ T-helper-17 (TH17) cells undergo active (presumably antigen-driven) expansion towards the end of the trajectory, and are characterized by good effector functions, while in critical COVID-19 they remain more naïve. Vice versa, CD4+ T-cells with T-helper-1 characteristics (TH1-like) and CD8+ T-cells expressing exhaustion markers (TEX-like) are enriched halfway their trajectories in mild COVID-19, where they also exhibit good effector functions, while in critical COVID-19 they show evidence of inflammation-associated stress at the end of their trajectories. Monocyte-to-macrophage trajectories show that chronic hyperinflammatory monocytes are enriched in critical COVID-19, while alveolar macrophages, otherwise characterized by anti-inflammatory and antigen-presenting characteristics, are depleted. In critical COVID-19, monocytes contribute to an ATP-purinergic signaling-inflammasome footprint that could enable COVID-19 associated fibrosis and worsen disease-severity. Finally, viral RNA-tracking reveals infected lung epithelial cells, and a significant proportion of neutrophils and macrophages that are involved in viral clearance