Subversion of innate immune responses by Brucella through the targeted degradation of the TLR signaling adapter, MAL. Academic Article uri icon

abstract

  • Gram-negative bacteria belonging to the Brucella species cause chronic infections that can result in undulant fever, arthritis, and osteomyelitis in humans. Remarkably, Brucella sp. genomes encode a protein, named TcpB, that bears significant homology with mammalian Toll/IL-1 receptor domains and whose expression causes degradation of the phosphorylated, signal competent form of the adapter MyD88-adapter-like (MAL). This effect of TcpB is mediated through its box 1 region and has no effect on other TLR adapter proteins such as MyD88 or TIR-domain containing adapter protein-inducing IFNbeta. TcpB also does not affect a mutant, signal-incompetent form of MAL that cannot be phosphorylated. Interestingly, the presence of TcpB leads to enhanced polyubiquitination of MAL, which is likely responsible for its accelerated degradation. A Brucella abortus mutant lacking TcpB fails to reduce levels of MAL in infected macrophages. Therefore, TcpB represents a unique pathogen-derived molecule that suppresses host innate-immune responses by specifically targeting an individual adapter molecule in the TLR signaling pathway for degradation.

published proceedings

  • J Immunol

author list (cited authors)

  • Sengupta, D., Koblansky, A., Gaines, J., Brown, T., West, A. P., Zhang, D., ... Ghosh, S

citation count

  • 89

complete list of authors

  • Sengupta, Dola||Koblansky, Alicia||Gaines, Jennifer||Brown, Tim||West, A Phillip||Zhang, Dekai||Nishikawa, Tak||Park, Sung-Gyoo||Roop, R Martin||Ghosh, Sankar

publication date

  • December 2009