Subversion of Toll-like receptor signaling by a unique family of bacterial Toll/interleukin-1 receptor domain–containing proteins
| Autor: | Nuria Rodriguez, Andreas Wieser, Dominik Stappert, Christine Cirl, Nina Wantia, Hermann Wagner, Susanne Duerr, Manisha Yadav, Sören Schubert, Hans Fischer, Catharina Svanborg, Thomas Miethke |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Virulence Factors
Molecular Sequence Data Virulence Interleukin-1 receptor Biology medicine.disease_cause General Biochemistry Genetics and Molecular Biology Cell Line Microbiology Mice Escherichia coli medicine Animals Humans Amino Acid Sequence Escherichia coli Infections Toll-like receptor Innate immune system Pyelonephritis Sequence Homology Amino Acid Escherichia coli Proteins Macrophages Toll-Like Receptors Receptors Interleukin-1 Signal transducing adaptor protein General Medicine Brucella Immunity Innate Protein Structure Tertiary Genes Bacterial Myeloid Differentiation Factor 88 Urinary Tract Infections Signal transduction Signal Transduction |
| Zdroj: | Nature Medicine. 14:399-406 |
| ISSN: | 1546-170X 1078-8956 |
| DOI: | 10.1038/nm1734 |
| Popis: | Pathogenic microbes have evolved sophisticated molecular strategies to subvert host defenses. Here we show that virulent bacteria interfere directly with Toll-like receptor (TLR) function by secreting inhibitory homologs of the Toll/interleukin-1 receptor (TIR) domain. Genes encoding TIR domain containing-proteins (Tcps) were identified in Escherichia coli CFT073 (TcpC) and Brucella melitensis (TcpB). We found that TcpC is common in the most virulent uropathogenic E. coli strains and promotes bacterial survival and kidney pathology in vivo. In silico analysis predicted significant tertiary structure homology to the TIR domain of human TLR1, and we show that the Tcps impede TLR signaling through the myeloid differentiation factor 88 (MyD88) adaptor protein, owing to direct binding of Tcps to MyD88. Tcps represent a new class of virulence factors that act by inhibiting TLR- and MyD88-specific signaling, thus suppressing innate immunity and increasing virulence. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|