Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in patients treated with allogeneic hematopoietic stem cell transplantation (HSCT). Posttransplant immunosuppressive drugs incompletely control GVHD and increase susceptibility to opportunistic infections. In this study, we used flagellin, a TLR5 agonist protein (∼50 kDa) extracted from bacterial flagella, as a novel e...

Salmonella typhimurium is a gram-negative enteric pathogen that invades the mucosal epithelium and is associated with diarrheal illness in humans. Flagellin from S. typhimurium and other gram-negative bacteria has been shown to be the predominant proinflammatory mediator through activation of the basolateral Toll-like receptor 5 (TLR5). Recent evidence has shown that prior exposure can render i...

The TLR5 agonist flagellin induces innate and adaptive immune responses in a MyD88-dependent manner and is under development as a vaccine adjuvant. In vitro studies indicate that, compared with other bacteria-derived adjuvants, flagellin is a very potent activator of proinflammatory gene expression and cytokine production from cells of nonhemopoietic origin. However, the role of nonhemopoietic ...

Flagellin is a wide-spread bacterial virulence factor sensed by the membrane-bound Toll-like receptor 5 (TLR5) and by the intracellular NAIP5/NLRC4 inflammasome receptor. TLR5 recognizes a conserved region within the D1 domain of flagellin, crucial for the interaction between subunits in the flagellum and for bacterial motility. While it is known that a deletion of the D0 domain of flagellin, w...

BACKGROUND Flagellin is the main structural protein of the flagella of many pathogens including Salmonella typhimurium. It is a potent trigger of innate immune responses that enhance adaptive immune responses to a variety of protein antigens. Flagellin has intrinsic adjuvant activity mediated through toll-like receptor (TLR) 5 and is an attractive candidate for highly effective vaccine adjuvant ...

Outer membrane vesicles (OMVs) isolated from Salmonella Typhimurium are potentially useful for developing subunit vaccines because of high immunogenicity and protective efficacy. However, flagella might remain in OMV pellets following OMV purification, resulting in non-essential immune responses and counteraction of bacterial protective immune responses when developing a vaccine against infecti...

Flagellin subunits are important inducers of host immune responses through activation of TLR5 when extracellular and the inflammasome if cytosolic. Our previous work demonstrated that systemic immunization of cattle with flagella generates systemic and mucosal IgA responses. The IgA response in mice is TLR5-dependent and TLR5 can impact on the general magnitude of the adaptive response. However...

The opportunistic pathogen Pseudomonas aeruginosa can cause severe infections in patients suffering from disruption or disorder of the skin barrier as in burns, chronic wounds, and after surgery. On healthy skin P. aeruginosa causes rarely infections. To gain insight into the interaction of the ubiquitous bacterium P. aeruginosa and healthy human skin, the induction of the antimicrobial protein...

Recognition of specific pathogen associated molecular patterns (PAMPs) is mediated primarily by members of the Toll-like receptor (TLR) family. Stimulation through these receptors results in quantitative and qualitative changes in antigen presentation and cellular activation, thereby linking innate and adaptive immunity. Consequently, the incorporation of TLR-ligands into vaccines could result ...

Toll-like receptors (TLRs) are innate immune receptors that sense a variety of pathogen-associated molecular patterns (PAMPs) by interacting with them and subsequently initiating signal transduction cascades that elicit immune responses. TLR11 has been shown to interact with two known protein PAMPs: Salmonella and E. coli flagellin FliC and Toxoplasma gondii profilin-like protein. Given the hig...