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Bacterial TIR-containing proteins and host innate immune system evasion

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Abstract

The innate immune system provides the first line of host defence against invading pathogens. Key to upregulation of the innate immune response are Toll-like receptors (TLRs), which recognize pathogen-associated molecular patterns (PAMPs) and trigger a signaling pathway culminating in the production of inflammatory mediators. Central to this TLR signaling pathway are heterotypic protein–protein interactions mediated through Toll/interleukin-1 receptor (TIR) domains found in both the cytoplasmic regions of TLRs and adaptor proteins. Pathogenic bacteria have developed a range of ingenuous strategies to evade the host immune mechanisms. Recent work has identified a potentially novel evasion mechanism involving bacterial TIR domain proteins. Such domains have been identified in a wide range of pathogenic bacteria, and there is evidence to suggest that they interfere directly with the TLR signaling pathway and thus inhibit the activation of NF-κB. The individual TIR domains from the pathogenic bacteria Salmonella enterica serovar Enteritidis, Brucella sp, uropathogenic E. coli and Yersinia pestis have been analyzed in detail. The individual bacterial TIR domains from these pathogenic bacteria seem to differ in their modes of action and their roles in virulence. Here, we review the current state of knowledge on the possible roles and mechanisms of action of the bacterial TIR domains.

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Acknowledgments

This work was funded by the UK Ministry of Defence.

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Author notes

  1. Rohini R. Rana

    Present address: MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK

Authors and Affiliations

  1. Division of Molecular Biosciences, Imperial College London, South Kensington, London, SW7 2AZ, UK

    Rohini R. Rana, Minghao Zhang & Bernadette Byrne

  2. Department of Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, SP4 0JQ, UK

    Abigail M. Spear & Helen S. Atkins

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  1. Rohini R. Rana
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  2. Minghao Zhang
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  3. Abigail M. Spear
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  5. Bernadette Byrne
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Correspondence to Bernadette Byrne.

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Crown Copyright 2011. Published with the permission of the Defence Science and Technology Laboratory on behalf of the Controller of HMSO.

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Rana, R.R., Zhang, M., Spear, A.M. et al. Bacterial TIR-containing proteins and host innate immune system evasion. Med Microbiol Immunol 202, 1–10 (2013). https://doi.org/10.1007/s00430-012-0253-2

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  • DOI: https://doi.org/10.1007/s00430-012-0253-2

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