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The Clinical Importance of Botulinum Toxin as an Injected Protein
Published in Yates Yen-Yu Chao, Optimizing Aesthetic Toxin Results, 2022
C. botulinum employ flagella to move. Flagellin is contained in the fermentation product used as a starting material for purifying BoNT/A. If not completely removed (such as reported for Dysport® [Panjwani et al., 2008]), flagellin is a potent adjuvant capable of activating immune cells, including DCs, by binding to toll-like receptor 5 (Mizel et al. 2010).
Order Articulavirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
Wang BZ et al. (2012) developed the flagellin- and M2-enhanced influenza VLP vaccines with broad protective efficacy using the flagellin and M2e fusion. Thus, the authors designed a membrane-anchored fusion protein by replacing the hyperimmunogenic region of flagellin with four repeats of M2e and fusing it to a membrane anchor from HA. The fusion protein was incorporated into influenza virus M1-based VLPs. These VLPs retained TLR5 agonist activity comparable to that of soluble flagellin, while the mice immunized with the chimeric VLPs by either intramuscular or intranasal immunization showed high levels of systemic M2-specific antibody responses (Wang BZ et al. 2012).
Innate and Adaptive Immune Dysfunction and Necrotizing Enterocolitis
Published in David J. Hackam, Necrotizing Enterocolitis, 2021
Paula Osterhout, Christina S. Kim, Erika C. Claud
For organisms that breach the intestinal mucosal barrier, there are enterocyte defense responses. Pattern recognition receptors (PRRs) recognize generalized components of microbes or signals from injured cells. A key highly conserved family of PRRs are called the toll-like receptors (TLRs). Each TLR recognizes a specific bacterial product (18, 19). For example, TLR-2 recognizes products of gram-positive organisms such as peptidoglycan and lipoteichoic acid. TLR-4 recognizes lipopolysaccharide from gram-negative organisms. TLR-5 recognizes flagellin, a proinflammatory subunit of bacteria flagella. TLR-9 recognizes CpG/bacterial DNA (20, 21). TLRs are required to maintain intestinal homeostasis, protect against intestinal injury, and limit bacterial translocation. Binding of any of these receptors leads to activation of nuclear factor kappaB (NF-κB).
Hepatoprotective effect of the radiation countermeasure flagellin in the long term after irradiation of mice
Published in International Journal of Radiation Biology, 2023
Lyudmila P. Sycheva, Lev M. Rozhdestvenskii, Nina I. Lisina, Tatyana G. Shliakova, Valery V. Zorin, Kseniya Yu. Romanova
A study of radiation countermeasures on a model of mice irradiated with gamma radiation at a low dose rate (10 μG/min) was began in the Institute in 2014 (Rozhdestvenskii et al. 2017). The advantage of low-intensity irradiation is the possibility of using high doses of radiation without the danger of early radiation death of animals. This model was used to study the well-known radiation countermeasures betaleukin and riboxin in the long term after exposure, and their antiradiation effect was shown in mice (γ-H2AX and DNA comets were evaluated in spleen cells) 4, 6, and 8 months after irradiation (Vorobyeva et al. 2016; Rozhdestvenskii et al. 2017). It was important to evaluate the effectiveness of radiation countermeasure at the cellular level in the long term after exposure to γ-radiation using the classical micronucleus assay on polychromatic bone marrow erythrocytes (rapidly dividing cell population) and on mouse hepatocytes (slowly dividing cell population). Betaleukin restored to the control level the ploidy of hepatocytes, which was sharply reduced in irradiated mice 10 months after exposure (Sycheva and Rozhdestvenskii 2020). It can be assumed that flagellin is also characterized by such properties.
Gut-derived bacterial flagellin induces beta-cell inflammation and dysfunction
Published in Gut Microbes, 2022
Torsten P.M. Scheithauer, Hilde Herrema, Hongbing Yu, Guido J. Bakker, Maaike Winkelmeijer, Galina Soukhatcheva, Derek Dai, Caixia Ma, Stefan R. Havik, Manon Balvers, Mark Davids, Abraham S. Meijnikman, Ömrüm Aydin, Bert-Jan H. van den Born, Marc G. Besselink, Olivier R. Busch, Maurits de Brauw, Arnold van de Laar, Clara Belzer, Martin Stahl, Willem M. de Vos, Bruce A. Vallance, Max Nieuwdorp, C. Bruce Verchere, Daniël H. van Raalte
Flagellum is a virulence factor that enables bacteria to move within the intestine and even adhere to the intestinal wall, a process called encroachment.20 Flagellin is expressed by a variety of bacteria. Here, we used a commercially available pure flagellin from Salmonella typhimurium to avoid impurities from other bacterial components such as LPS. Both bacteria, S. typhimurium and E. cloacae, belong to the family Enterobacteriaceae. We see similar effects for both flagellin types. Flagellin fully reproduced the beta-cell phenotype of E. cloacae. A causal role for flagellin was observed in E. cloacae with flagellin knockout, where the effects on inflammation, hypersecretion and reduced insulin content were strongly diminished. Strengthening the role of flagellin, mice that were injected with flagellin exhibited a similar beta-cell phenotype. However, we cannot deduce whether this effect was directly on beta cells or a secondary response on other cells.
Compensatory intestinal immunoglobulin response after vancomycin treatment in humans
Published in Gut Microbes, 2021
Torsten P. M. Scheithauer, Guido J. Bakker, Maaike Winkelmeijer, Mark Davids, Max Nieuwdorp, Daniël H. van Raalte, Hilde Herrema
Flagellin facilitates bacterial motility, adhesion to the epithelium, and biofilm formation.31,32 The latter is an important bacterial defense system.33 Interestingly, K. pneumoniae, a common biofilm-forming bacterium that expresses flagella34 but circumvents IgA coating in our dataset. In contrast, E. coli, also flagellum-bearing, is heavily coated with IgA.35 Therefore, the potential to express virulence factors such as flagellin does not necessarily implicate IgA coating. Expression of flagella and surface antigens recognized by IgA depends on environmental factors. In in vitro settings, most bacteria display vastly different patterns of surface antigens.11 Although our data set did not allow testing of this difference, antibiotic treatment might increase bacterial interaction with intestinal cells and increase the odds for bacterial infections.