Anthrax toxin evades Toll-like receptor recognition, whereas its cell wall components trigger activation via TLR2/6 heterodimers
Article first published online: 26 JUL 2007
Volume 9, Issue 12, pages 2880–2892, December 2007
How to Cite
Triantafilou, M., Uddin, A., Maher, S., Charalambous, N., Hamm, T. S. C., Alsumaiti, A. and Triantafilou, K. (2007), Anthrax toxin evades Toll-like receptor recognition, whereas its cell wall components trigger activation via TLR2/6 heterodimers. Cellular Microbiology, 9: 2880–2892. doi: 10.1111/j.1462-5822.2007.01003.x
- Issue published online: 13 AUG 2007
- Article first published online: 26 JUL 2007
- Received 6 March, 2007; revised 4 June, 2007; accepted 6 June, 2007.
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.