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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.
Nasopharyngeal and oral immune system
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Hiroshi Kiyono, Kohtaro Fujihashi
Bacterial flagellin, the ligand for TLR5, also has been used as adjuvant and vaccine delivery systems. BALB/c mice subcutaneously immunized with a flagellin-enhanced green fluorescent protein (EGFP) fusion protein results in the effective generation of EGFP-specific T-cell responses. Further, Salmonella typhimurium flagellin enhances CD4+ T-cell responses to cointravenously administered OVA peptides. Nasal immunization with purified flagellin from Salmonella enterica serovar Enteritidis alone or conjugated to starch microparticles induces mixed TH1/TH2-type response and high flagellin-specific SIgA Ab titers in fecal extracts. Vibrio vulnificus major flagellin coadministered with tetanus toxoid vaccine induces significant tetanus toxoid-specific IgA Ab responses in both mucosal and systemic compartments and IgG Ab responses in the systemic compartment. The flagella filament structural protein (FliC) of S. enteritidis stimulates human β defensin-2 mRNA in Caco-2 cells by mechanisms involving mitogen-activated protein kinase. In this regard, nasal administration of human neutrophil peptide defensins enhances systemic IgG and promotes B- and T-cell interactions to link innate immunity with the adaptive immune system. These findings underscore the importance of a full molecular understanding of the innate and acquired immune response initiated by microorganisms, which will facilitate the development of more appropriate, potent, and safe nasal adjuvants.
Genetically Engineered Oncolytic Salmonella typhimurium
Published in Ananda M. Chakrabarty, Arsénio M. Fialho, Microbial Infections and Cancer Therapy, 2019
Bacterial flagellin from both gram-positive and gram-negative bacteria is the natural ligand of toll-like receptor 5 (TLR5), and activation of the TLR5 signaling pathway mobilizes nuclear factor (NF)-κB and induces the production of TNF-α. Activation of TLR5 by purified flagellin results in the regression of TLR5-positive breast and colon cancers [38, 39]. However, this strategy is restricted to TLR5-positive cancer models and multiple injections are required. We recently used an engineered S. typhimurium to overexpress heterologous flagellin, enhancing cancer immunotherapy [6]. Because high concentrations of bacteria accumulate in tumors, and these bacteria continuously secrete abundant amounts of flagellin after induction, their anticancer effects are markedly enhanced. Flagellins in V. vulnificus flagellum are encoded by six flagellin structural genes (flaA, flaB, flaF, flaC, flaD, and flaE), with FlaB being the most crucial building block [40]. FlaB has been applied as an adjuvant in combination with human papillomavirus (HPV) E6/E7 antigens to treat both subcutaneous and orthotopic genital cancer models, inducing robust anticancer immunity and suggesting that FlaB is an excellent adjuvant for cancer immunotherapy [41, 42]. FlaB has high binding affinity to TLR5 and was more potent in stimulating TLR5 signaling than Salmonella flagellin FliC [40].
Effect of Huangqin decoction on regulating intestinal flora in colitis mice characterized as inhibition of the NOD2-dependent pathway
Published in Pharmaceutical Biology, 2022
Shaowei Huang, Jinrong He, Yanping Chen, Xiaojing Wang, Yanyang Li, Yulin Su, Ruyan Wen, Xiuling Li, Guanghua Yang, Shuang Luo, Lian Zhou, Xia Luo
It is reported that pathogen-associated molecular patterns (PAMPs), mainly derived from intestinal bacteria, excessively trigger the immune system, releasing pro-inflammatory cytokines and further destroying the intestinal barrier (Geremia et al. 2014; Wang et al. 2019). PAMPs, like lipopolysaccharides (LPS), flagellin, muramyl dipeptide (MDP), are recognized by pattern recognition receptors (PRRs), which activates PRRs (LPS combined with TLR4, flagellin combined with TLR5, and MDP combined with NOD2) and their downstream signalling pathways to release inflammatory cytokines, recruit phagocytic cells, and regulate dendritic cells. In a study of PRRs, the nucleotide-binding oligomerization domain-containing protein 2 (NOD2)-dependent pathway is found to be influential among multiple inflammatory signalling pathways, and Nod2 is the first susceptible gene found to be associated with IBD (Germain et al. 2016). The number of bacteria adhering to the intestinal mucosa increased in UC patients with NOD2 gene mutation. In addition, some studies also indicate that the expression of Toll-like receptor (TLR) 4 and TLR5 increased in UC mice (Luo et al. 2018; Wang et al. 2019).
Vancomycin prevents fermentable fiber-induced liver cancer in mice with dysbiotic gut microbiota
Published in Gut Microbes, 2020
Vishal Singh, Beng San Yeoh, Ahmed A. Abokor, Rachel M. Golonka, Yuan Tian, Andrew D. Patterson, Bina Joe, Mathias Heikenwalder, Matam Vijay-Kumar
All animal studies described were conducted as per institutional animal care and use committee (IACUC) approvals obtained from the Pennsylvania State University and the University of Toledo. Toll-like receptor 5 (TLR5) deficient (T5KO) mice were originally generated by Dr. Shizuo Akira, Japan on C57BL/6 background. These mice were bred and maintained under specific pathogen-free conditions at the Pennsylvania State University and at the University of Toledo. Mice were housed in cages (n = 5 mice/cage) containing corncob bedding (Bed-O-Cob, The Andersons Co.) and nestlets (cat# CABFM00088, Ancare), fed ad libitum (LabDiet 5020 for breeders and LabDiet 5001 for weaned mice) and given regular, non-acidified drinking water. Mice were housed at 23°C under a 12-h light/dark phase cycle.
The human gut microbiota: Metabolism and perspective in obesity
Published in Gut Microbes, 2018
Aline Corado Gomes, Christian Hoffmann, João Felipe Mota
Besides acting on the maturation of GALT, the commensal bacteria also prevent the intestinal colonization by pathogens. The gut microbiota improves the function of the epithelial barrier, while its absence decreases the production of antimicrobial peptides by Paneth cells. This event causes intestinal barrier dysfunction and increases bacterial translocation.22 Furthermore, bacteria-induced myeloid differentiation factor 88 (MyD88) signaling in the intestine increases epithelial cell IgA secretion. In addition, bacterial flagellin activates Toll-like receptors 5 (TLR5) from dendritic cells, and promotes the differentiation of B lymphocytes into IgA-producing cells23 IgA binds to the microbial antigens, neutralizes the activity of the pathogens, and prevents infection.24