title: Anthrax toxin evades Toll-like receptor recognition, whereas its cell wall components trigger activation via TLR2/6 heterodimers.
abstract: Bacillus anthracis is a Gram-positive bacillus that is the causative agent of anthrax. The virulence of the bacillus is partly due to the production of a tripartite virulence factor: protective antigen (PA), lethal factor (LF) and edema factor (EF). Recognition of the bacillus and its toxins by the innate immune system is likely to play a key role following infection. In this study we set out to investigate whether anthrax cell wall (ACW) components as well as the lethal toxin are sensed by Toll-like receptors (TLRs). Our data suggest that ACW components as well as PA are sensed by TLR2/6 heterodimers triggering an inflammatory response. This recognition takes place on the cell surface within specialized microdomains for ACW, whereas PA seems to trigger responses intracellularly. Interestingly, LF does not trigger a pro-inflammatory response, and when combined with PA, the complex is not sensed by the innate immune system. Overall our data suggest that TLR2/6 heterodimers are responsible for sensing the ACW and PA, whereas the formation of the subsequent toxin (LF + PA) seems to evade detection by the innate immune system contributing to the virulence of the toxin.
authors.affiliation: Infection and Immunity Group, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, UK.
authors.forename: Martha
authors.initials: M
authors.lastname: Triantafilou
authors.forename: Ahmed
authors.initials: A
authors.lastname: Uddin
authors.forename: Sebastien
authors.initials: S
authors.lastname: Maher
authors.forename: Nicholas
authors.initials: N
authors.lastname: Charalambous
authors.forename: Thomas S C
authors.initials: TS
authors.lastname: Hamm
authors.forename: Ahmad
authors.initials: A
authors.lastname: Alsumaiti
authors.forename: Kathy
authors.initials: K
authors.lastname: Triantafilou
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology*; D001408:Bacillus anthracis / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology*; D002460:Cell Line; D002473:Cell Wall / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D051216:Toll-Like Receptor 6 / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C495342:TLR2 protein, human; C495368:TLR6 protein, human; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; C030325:anthrax toxin