Cell and Tissue Research

, Volume 372, Issue 1, pp 1–11 | Cite as

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

  • Glenn Hamonic
  • J. Alex Pasternak
  • Heather L. Wilson


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.


Toll-like receptor Mucosal Innate immunity Epithelial Localization 



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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Glenn Hamonic
    • 1
    • 2
  • J. Alex Pasternak
    • 1
  • Heather L. Wilson
    • 1
    • 2
  1. 1.Vaccine & Infectious Disease Organization-International Vaccine Center (VIDO-InterVac)University of SaskatchewanSaskatoonCanada
  2. 2.Department of Veterinary Microbiology, Western College of Veterinary MedicineUniversity of SaskatchewanSaskatoonCanada

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