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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).
Immunology of Allergic Diseases
Published in Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial, Textbook of Allergy for the Clinician, 2021
Besides TSLP there are two other EC derived cytokines that have a TH2 polarizing effect. They are the IL-1 and IL-18 family member IL-33 acting through its receptor, ST2 and IL-25 which is one of the six members of the IL-17 cytokine family. TSLP, IL-33 and IL-25 are generated by the airway epithelium in response to cytotoxic epithelial injury as well as by activation of PRRs such as TLR3 and TLR5. The ligand for TLR3 is a viral double-stranded RNA and for TLR5 the ligand is bacterial flagellin. IL-33 functions as an alarmin to alert the immune system to physical stress or infection. IL-25 and IL-33 activate the recently recognized, innate type-2 immune effector leukocyte, the nuocyte. The nuocyte functions as the connecting link between the innate and adaptive TH2 response, in that activated nuocytes secrete IL-4, IL-5, IL-9 and IL-13 all of which cause B cell activation, increased IgE production and eosinophilia as well as promoting goblet cell hypertrophy and increase airway hyper responsiveness— features that are an integral part of allergic inflammation (Holgate 2012).
Urinary Tract Infections (UTI)
Published in Manit Arya, Taimur T. Shah, Jas S. Kalsi, Herman S. Fernando, Iqbal S. Shergill, Asif Muneer, Hashim U. Ahmed, MCQs for the FRCS(Urol) and Postgraduate Urology Examinations, 2020
Nish Bedi, Ali Omar, Jas S. Kalsi
Pathogen recognition receptors Toll-like receptor (TLR) 4 and TLR5 appear the most important receptors for endotoxins, with TLR4 recognising lipopolysaccharide (LPS), as the major component of the cell wall in Gram-negative bacteria.
Toward a porcine in vivo model to analyze the pathogenesis of TLR5-dependent enteropathies
Published in Gut Microbes, 2020
Robert Pieper, Niels van Best, Kira van Vorst, Friederike Ebner, Monika Reissmann, Mathias W. Hornef, Marcus Fulde
Interestingly, variants in the TLR5 locus were also found in other animals, e.g. in the German shepherd dog. Notably, also here an association between inherited TLR5 dysfunction and protection from IBD and other enteropathies was established.25,26 Furthermore, the pig breed “Deutsche Landrasse” harbors an SNP in TLR5, which is inherited recessively on chromosome 10 and leads to a P402L amino acid change causing impaired recognition of Salmonella and flagellin, respectively.27 This SNP does not lead to an entirely dysfunctional TLR5 but has been shown to reduce downstream NF-κB activation by about one-third as compared to the wildtype TLR5 allele.28 Consistently, the impaired flagellin recognition in the pig may confer an increased susceptibility to flagellated bacteria, such as Salmonella Typhimurium and (entero-)pathogenic E. coli.29–31 The latter observation opens the possibility for further investigations of the functional role of TLR5-signaling in mucosal inflammation in a model that mimics the human situation more closely and may additionally allow the evaluation of potential preventive measures and therapeutic strategies. Pigs share key similarities with humans, such as body size, anatomical features, (patho-)physiological responses and diet.32 Also, the microbiota of humans is more similar to the microbiota of pigs than rodent animals.33 This is particularly important since microbiota alterations appear to play a functional role.12
Fecal transplantation for ulcerative colitis: current evidence and future applications
Published in Expert Opinion on Biological Therapy, 2020
Loris R. Lopetuso, Gianluca Ianiro, Jessica R. Allegretti, Stefano Bibbò, Antonio Gasbarrini, Franco Scaldaferri, Giovanni Cammarota
TLRs are expressed on cells within the intestinal mucosa, including IECs and more broadly, on lamina propria macrophages and dendritic cells [35–38]. TLR2, −4 and −5 are the major cell-surface sensors of bacterial lipopeptides, including LPS and flagellins, while TLR3, −7, −8 and −9 recognize nucleic acid motifs [39]. Among these, both human and murine studies have proposed the involvement of TLR5 and its ligand, the bacterial protein flagellin, in the modulation of innate and adaptive immune responses linked to IBD pathophysiology [40–43]. TLR5-knockout animals develop spontaneous colitis [44] and are more vulnerable to dextran sulfate sodium (DSS)-induced colitis, a T-cell independent, chemically induced model of epithelial damage and acute inflammation, primarily driven by innate immune responses [45]. Aberrant, elevated TLR5 expression is present in the ileal epithelium of SAMP1/YitFc (SAMP) mice, a spontaneous model of CD-like ileitis. It is increased in the presence of the gut microbiome, and when activated by bacterial flagellin leads to an impaired gut barrier integrity [46]. Together, these data represent a potential mechanistic pathway leading to the exacerbation and perpetuation of chronic gut inflammation in experimental IBD models and possibly, in IBD patients.
KMRC011, an agonist of toll-like receptor 5, mitigates irradiation-induced tissue damage and mortality in cynomolgus monkeys
Published in Journal of Immunotoxicology, 2020
Hong-Soo Lee, Doo-Wan Cho, Ji-Seok Han, Su-Cheol Han, Sang Keun Woo, Soo-Youn Jun, Woo-Jong Lee, Susie Yoon, Son-Il Pak, Sang-Jin Lee, Eunsol Seong, Eun-Jung Park
Toll-like receptors (TLR) are a family of transmembrane receptors that play a crucial role in innate immune defense mechanisms against pathogens (Takeda and Akira 2001). One in particular, TLR5, is involved in inflammatory responses. Over-activation of TLR5 subsequently leads to the onset of various diseases, in part, by stimulation of the production of NF-κB (nuclear factor κ-light-chain-enhancer of activated B-cells) and tumor necrosis factor (TNF)-α (Akira and Takeda 2004; Tarahomjoo 2014; Singh and Pollard 2015). NF-κB is important in that it helps to control tissue repair and cell survival by inhibiting apoptotic cell death; because of this function, it would appear that a promising approach in the development of radioprotective substances might be agents that target TLR5 and/or NF-κB (Krivokrysenko et al. 2015; Li et al. 2016).