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Recognizing conserved non-canonical localization patterns of toll-like receptors in tissues and across species

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Abstract

Toll-like receptors (TLR) 1, 2, 4, 5 and 6 were originally characterized as exclusively expressed on the cell surface and TLR 3, 7, 8 and 9 were said to be localized to the endosomes. However, continued research in this area shows that TLR localization may be altered across cell-types, and in response to stimulation, age or disease. Mucosal surfaces must remain tolerant to the commensal flora and thus intracellular or basal lateral localization of TLRs at mucosal surfaces may be necessary to prevent induction of an inflammatory response to commensal flora while still allowing the possibility for the receptors to prime an immune response when a pathogen has crossed the epithelial barrier. Here, we highlight the research specifying ‘non-canonical’ localization of TLRs in human and animal mucosal tissues and blood-derived cells, while excluding cultured polarized immortalized cells. Reports that only indicate TLR gene/protein expression and/or responsiveness to agonists have been excluded unless the report also indicates surface/intracellular distribution in the cell. Understanding the tissue- and species-specific localization of these specific pattern recognition receptors will lead to a greater appreciation of the way in which TLR ligands promote innate immunity and influence the adaptive immune response. A more comprehensive understanding of this information will potentially aid in the exploitation of the therapeutic or adjuvant potential of selectively localized TLRs and in opening new perspectives in understanding the basis of immunity.

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Acknowledgements

This review was funded by a Natural Sciences and Engineering Research Council of Canada (NSERC) grant awarded to Heather Wilson. Glenn Hamonic was supported by a Devolved Scholarship from the Department of Veterinary Microbiology at the Western College of Veterinary Medicine. Alex Pasternak was supported by a NSERC Postdoctoral Fellowship. This manuscript was published with approval of the director of VIDO-InterVac as journal series no 802.

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  1. Vaccine & Infectious Disease Organization-International Vaccine Center (VIDO-InterVac), University of Saskatchewan, 120 Veterinary Road, Saskatoon, SK, S7N 5E3, Canada

    Glenn Hamonic, J. Alex Pasternak & Heather L. Wilson

  2. Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Dr. Saskatoon, Saskatoon, SK, S7N 5B4, Canada

    Glenn Hamonic & Heather L. Wilson

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  1. Glenn Hamonic
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  2. J. Alex Pasternak
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  3. Heather L. Wilson
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Correspondence to Heather L. Wilson.

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Hamonic, G., Pasternak, J.A. & Wilson, H.L. Recognizing conserved non-canonical localization patterns of toll-like receptors in tissues and across species. Cell Tissue Res 372, 1–11 (2018). https://doi.org/10.1007/s00441-017-2767-9

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  • DOI: https://doi.org/10.1007/s00441-017-2767-9

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