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Salmonella enterica serovar Typhi impairs CD4 T cell responses by reducing antigen availability.

Salmonella enterica serovar Typhi is associated with a disseminated febrile illness in humans, termed typhoid fever, while Salmonella enterica serovar Typhimurium causes localized gastroenteritis in immunocompetent individuals. One of the genetic differences between both pathogens is the presence in S. Typhi of TviA, a regulatory protein that shuts down flagellin (FliC) expression when bacteria transit from the intestinal lumen into the intestinal mucosa. Here we investigated the consequences of TviA-mediated flagellum gene regulation on flagellin-specific CD4 T cell responses in a mouse model…

A self-adjuvanted nanoparticle based vaccine against infectious bronchitis virus.

Infectious bronchitis virus (IBV) affects poultry respiratory, renal and reproductive systems. Currently the efficacy of available live attenuated or killed vaccines against IBV has been challenged. We designed a novel IBV vaccine alternative using a highly innovative platform called Self-Assembling Protein Nanoparticle (SAPN). In this vaccine, B cell epitopes derived from the second heptad repeat (HR2) region of IBV spike proteins were repetitively presented in its native trimeric conformation. In addition, flagellin was co-displayed in the SAPN to achieve a self-adjuvanted effect. Three grou…

Molecular genetic basis for complex flagellar antigen expression in a triphasic serovar of Salmonella.

Strains of most Salmonella serovars produce either one (monophasic) or two (diphasic) antigenic forms of flagellin protein, but strains capable of expressing three or more serologically distinct flagellins ("complex" serovars) have occasionally been reported. A molecular genetic analysis of a triphasic strain of the normally diphasic serovar Salmonella rubislaw revealed that it has three flagellin genes, including the normal fliC (phase 1) and fljB (phase 2) chromosomal genes encoding type r and type e,n,x flagellins, respectively, and a third locus (herein designated as flpA) that is located …

Toll-like receptor 5 agonist is a potent adjuvant for intradermal vaccination.

Flagellin, the key structural protein of bacterial flagella, is known to stimulate Toll-like receptor 5 (TLR5) signaling, making it an effective adjuvant for nasal, intramuscular, or subcutaneous routes of vaccination. Here, we investigate the potential of intradermal flagellin delivery to enhance adaptive immunity in mouse and pig models. Our study shows that intradermal administration of flagellin enhances systemic antibody responses to co-administered antigens in a TLR5-dependent manner. Transcriptional analysis of mouse and pig skin revealed that flagellin induces an early pro-inflammatory…

Divergent immune responses to commensal bacteria bearing distinct motility signatures.

Adaptive immune responses to commensal flagellins are hallmarks of Crohn's disease (CD), but it is unclear whether flagellins themselves promote inflammation or whether flagellated commensals can also be colitogenic. Here, we show that the arrangement of motility loci and the diversity of encoded flagellins can separate flagellated gut-derived Clostridia into at least two functionally distinct groups. In gnotobiotic mice, both groups induce tolerogenic responses, but only one group promoted tissue inflammation after barrier disruption. Specific flagellins expressed by members of this proinflam…

Neutrophil subsets enhance the efficacy of host-directed therapy in pneumococcal pneumonia.

Host-directed therapy, using nasal administration of the Toll-like receptor 5 agonist flagellin in combination with antibiotics, has proven effective against pneumococcal pneumonia. In this study, we investigated the immune mechanisms underlying the therapy-induced protective effects. Transcriptomic analysis of lung tissue during infection revealed that flagellin not only enhanced pathways associated with myeloid cell infiltration into the airways and antimicrobial functions, but also promoted the early and transient mobilization of neutrophils and inflammatory monocytes. Neutrophils were iden…

Toll-like receptor 5 protects against nonsteroidal anti-inflammatory drug-induced enteropathy in mice.

BACKGROUND AND AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause small intestinal injury, which largely depends on the presence of gut bacteria and the immune responses triggered by them. While previous studies have emphasised the role of Toll-like receptor 4 (TLR4) and TLR2 in enteropathy, the functional significance of TLR5, a receptor for bacterial flagellin, remains elusive. Thus, we aimed to assess the impact of TLR5 activation and inhibition on NSAID enteropathy in mice. MATERIALS AND METHODS: Enteropathy was induced using indomethacin (IND). Mucosal injury, inflammation and…

Delivery of class I and class II MHC-restricted T-cell epitopes of listeriolysin of Listeria monocytogenes by attenuated Salmonella.

Using a Salmonella vaccine-Listeria infection model of intracellular infection, we studied the capacity of an attenuated strain of Salmonella carrying T-cell epitopes of listeriolysin (LLO) of L. monocytogenes to elicit epitope-specific T-cell responses. Class II (LLO 215-226) or class I (LLO 91-99) MHC-restricted T-cell epitopes of LLO were inserted within a central, hypervariable domain of the flagellin protein of an attenuated delta aroA Salmonella dublin strain. T cells from Listeria-immunized mice were activated by lysates or heat-killed preparations of Salmonella construct expressing the…

A Study on Campylobacter jejuni and Campylobacter coli through Commercial Broiler Production Chains in Thailand: Antimicrobial Resistance, the Characterization of DNA Gyrase Subunit A Mutation, and Genetic Diversity by Flagellin A Gene Restriction Fragment Length Polymorphism.

Contaminated poultry meat is regarded as the main source of human campylobacteriosis. During September 2014 and February 2015, breeder flock … ere typed with the use of polymerase chain reaction-restriction fragment length polymorphism of the flagellin A gene (flaA-RFLP) to determine their genetic relationships. Ten distinct clusters were recognized by flaA-RFLP typing. The results showed that horizontal transmission was the major route of Campylobacter transmission in this study. In conclusion, t …

Sequence Analyses and Phenotypic Characterization Revealed Multidrug Resistant Gene Insertions in the Genomic Region Encompassing Phase 2 Flagellin Encoding fljAB Genes in Monophasic Variant Salmonella enterica Serovar 4,5,12:i:- Isolates From Various Sources in Thailand.

Salmonella enterica serovar 4,5,12:i:- (S. 4,5,12:i:-), a monophasic variant of Salmonella Typhimurium (STm) lacking the phase 2 flagellin encoding genes fljAB, has become increasingly prevalent worldwide. The increasing trends in multidrug resistant (MDR) S. 4,5,12:i:- prevalence also pose an important global health threat. Though many reports have characterized phenotypic and genotypic drug resistance of this serovar, few studies have characterized antimicrobial resistance of this serovar in Thailand. In this study, 108 S. 4,5,12:i:- isolates from various sources in Thailand and four interna…

Expression and characterization of flagella in nonmotile enteroinvasive Escherichia coli isolated from diarrhea cases.

We report that enteroinvasive Escherichia coli (EIEC) serotypes considered to be nonmotile produce an unusually large (77 kDa) flagellin that is assembled into functional flagellum filaments that allow the bacteria to swim in modified motility agar. The EIEC flagellin showed N-terminal identity to most common enterobacterial flagellins, especially those of the E. coli H7 serotype. These data are important in terms of the epidemiology, evolution, and biology of EIEC.

Microbe-associated molecular patterns differentially mediate carcinogenic alterations of the breast tissue in the context of obesity.

Obesity is a risk factor for breast cancer. Obesity alters the microbiome and microbiome perturbations are reported in breast cancer patients. Yet, the impact of obesity-mediated microbial shifts on breast cancer risk remains unclear. Here, we investigate the effect of microbial-associated molecular pattern (MAMP) signaling on genome instability and inflammation. We show in human samples that obesity chronically elevates breast tissue levels of two MAMPs: lipopolysaccharide (LPS) and flagellin. In contrast, obesity was not associated with chronic elevations in lipoteichoic acid (LTA). Injectio…

Recombinant immunoblot in the serodiagnosis of Lyme borreliosis. Comparison with indirect immunofluorescence and enzyme-linked immunosorbent assay.

A recombinant immunoblot was developed for detection of IgM and IgG antibodies in patients with Lyme borreliosis. The recombinant antigens were the chromosomal-encoded Borrelia burgdorferi proteins p100, the flagellin and an internal flagellin fragment thereof as well as the plasmid-encoded outer surface proteins A (OspA) and C (OspC). A panel of 144 sera from patients with Lyme borreliosis (erythema migrans, n = 31; neuroborreliosis state II, n = 60; Lyme arthritis, n = 24 and acrodermatitis chronica atrophicans, n = 19) have been investigated and the results have been compared to the immunof…

TLR5 versus TLR7/8 agonist-dependent modulation of the early gene expression response to inactivated influenza virus vaccine in newborn nonhuman primates.

There is an urgent need for strategies that can improve vaccine immunogenicity, especially for vulnerable populations such as newborns and young infants. Growing evidence supports Toll-Like Receptor agonists (TLRa) as potent stimulatory molecules to increase vaccine efficacy. We have previously demonstrated that the inclusion of either flagellin (TLR5a) or R848 (TLR7/8a) in an inactivated influenza virus vaccine can improve responses in newborn NHP, with R848 being superior at providing protection upon challenge. This study aimed to identify early immune events triggered by either inactivated …

MicroRNA-5112 Targets IKKγ to Dampen the Inflammatory Response and Improve Clinical Symptoms in Both Bacterial Infection and DSS-Induced Colitis.

Inflammation is a double-edged sword that can be induced by various PAMPs, resulting in the control of infection by invading pathogens or injuries. The inflammatory response requires strict and precise control and regulation. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression via translational inhibition or mRNA degradation. However, the role of miRNAs in inflammation induced by flagellin (ligand of TLR5) has yet to be fully determined. In this study, we identified differentially expressed miRNAs in murine bone marrow-derived dendritic cells (BMDCs) between fla…

H9724, моноколональная антитела к флагселлину Боррелии Бурдорфери, связывается с тепловым шоковым белком 60 (HSP60) в живых нейробластомных клетках: потенциальная роль HSP60 в гормональном сигналировании и в аутоиммунном патогенезе от нейропатии болезни Лайма.

Хотя Борелия Бурдорфери, причинно-следственный агент болезни Лайма, находится на месте многих проявлений заболеваний, местная инфекция, возможно, не объясняет всех ее особенностей. B. Burgdorferi's zangellin-reacts с компонентом периферического нервного аксона, который ранее был идентифицирован как протеин от теплового удара 60 (HSP60). Перекрестные эпитопы связаны моноколональным антителом с флагселлином Б. Бурдорфери, H9724. Добавление H9724 в нейробластомные культуры блокирует в vitro спонтанный и пептидный фактор роста-стимулированный нейротогенез. Выход H9724 позволяет вернуться к нормаль

Совпадение в аннотации оригинала
Although Borrelia burgdorferi, the causative agent of Lyme disease, is found at the site of many disease manifestations, local infection may not explain all its features. B. burgdorferi's flagellin cross-reacts with a component of human peripheral nerve axon, previously identified as heat shock protein 60 (HSP60). The cross-reacting epitopes are bound by a m…

Human gut flagellome profiling using FlaPro reveals TLR5-related phenotype-specific alterations in IBD.

Flagellin, the structural protein of bacterial flagella, activates the innate immune receptor Toll-like receptor 5 (TLR5). However, the ability of different flagellins to bind and stimulate TLR5 varies widely, suggesting that the composition of an individual's flagellin repertoire, defined as flagellome, may influence host-microbiome interactions and inflammation. Here, we developed FlaPro, a computational pipeline for quantification and functional annotation of human gut flagellomes. Functional categories in FlaPro are derived from a machine learning model trained on experimentally characteri…

Structural diversity and clustering of bacterial flagellar outer domains.

Supercoiled flagellar filaments function as mechanical propellers within the bacterial flagellum complex, playing a crucial role in motility. Flagellin, the building block of the filament, features a conserved inner D0/D1 core domain across different bacterial species. In contrast, approximately half of the flagellins possess additional, highly divergent outer domain(s), suggesting varied functional potential. In this study, we report atomic structures of flagellar filaments from three distinct bacterial species: Cupriavidus gilardii, Stenotrophomonas maltophilia, and Geovibrio thiophilus. Our…

A repertoire of high-affinity monoclonal antibodies specific to S. typhi: as potential candidate for improved typhoid diagnostic.

Typhoid fever is a significant global health problem with highest burden on the developing world. The severity of typhoid is often underestimated, and currently available serological diagnostic assays are inadequate due to lack in requisite sensitivity and specificity. This underlines an absolute need to develop a reliable and accurate diagnostics that would benefit long-term disease control and treatment and to understand the real disease burden. Here, we have utilized flagellin protein of S. typhi that is surface accessible, abundantly expressed, and highly immunogenic, for developing immuno…