title: To con protection: TIR-domain containing proteins (Tcp) and innate immune evasion.
abstract: The innate immune system provides the host's first line of defence against invading pathogens. Key to the stimulation of the innate immune response is pattern-recognition receptors (PRRs), such as Toll-like receptors (TLRs), which recognize microbial-associated molecular patterns (MAMPs). Binding of MAMPs to TLRs triggers a signalling cascade resulting in the production of pro-inflammatory mediators. Central to this TLR signalling pathway are heterotypic protein-protein interactions mediated through Toll/interleukin-1 receptor (TIR) domains found in both the cytoplasmic regions of TLRs and several key adaptor proteins. Interestingly, TIR-domain containing proteins (Tcps) do not seem to be unique to the mammalian TLR system, but occurs in abundance in many biological forms. Recent evidence suggests that pathogenic bacteria have developed a range of ingenuous strategies to evade the host immune mechanisms involving Tcps. There is increasing evidence to suggest that these pathogen-encoded Tcps interfere directly with the TLR signalling pathway and thus inhibit the activation of NF-κB, with different modes of action and roles in virulence. Here, we review the current state of knowledge on the possible roles and mechanisms of action of bacterial encoded Tcp.
authors.affiliation: Molecular Immunology Group, Department of Pathology and Pathogen Biology, Royal Veterinary College, Hawkshead Lane, Hatfield AL9 7TA, UK.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Patterson
authors.forename: Dirk
authors.initials: D
authors.lastname: Werling
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology; D017434:Protein Structure, Tertiary; D017472:Receptors, Interleukin-1 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D051193:Toll-Like Receptors / Q000502:physiology*
chemical_list: D016328:NF-kappa B; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors
keywords: Innate Immunity; TIR domain; TIR-domain containing protein; TLR signalling pathway; Tcp