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Olfactory immunology: the missing piece in airway and CNS defence

Nature Reviews Immunology (2023)Cite this article

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Abstract

The olfactory mucosa is a component of the nasal airway that mediates the sense of smell. Recent studies point to an important role for the olfactory mucosa as a barrier to both respiratory pathogens and to neuroinvasive pathogens that hijack the olfactory nerve and invade the CNS. In particular, the COVID-19 pandemic has demonstrated that the olfactory mucosa is an integral part of a heterogeneous nasal mucosal barrier critical to upper airway immunity. However, our insufficient knowledge of olfactory mucosal immunity hinders attempts to protect this tissue from infection and other diseases. This Review summarizes the state of olfactory immunology by highlighting the unique immunologically relevant anatomy of the olfactory mucosa, describing what is known of olfactory immune cells, and considering the impact of common infectious diseases and inflammatory disorders at this site. We will offer our perspective on the future of the field and the many unresolved questions pertaining to olfactory immunity.

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Fig. 1: Heterogeneity of the upper respiratory tract: the olfaction fraction.
Fig. 2: Cell types and effector mechanisms in the olfactory mucosa.

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Acknowledgements

E.A.M. is supported by R01NS121067, R21DC021260 and R21AG074324, and by the Duke School of Medicine Whitehead Family Scholarship.

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    Sebastian A. Wellford & E. Ashley Moseman

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Glossary

Anosmia

The complete loss of smell, typically defined clinically by the University of Pennsylvania Smell Identification Test scores <19.

Blood–olfactory barrier

(BOB). A blood–endothelial barrier that prevents the movement of large molecules from circulation into the olfactory mucosa.

Dysosmia

A general term for an altered sense of smell.

Hyposmia

A reduced sense of smell, typically defined clinically by the University of Pennsylvania Smell Identification Test scores in the 19–33 range, although scoring can be adjusted by age and sex.

Olfactory binding proteins

Soluble proteins in the nasal mucus that bind to odourants to facilitate recognition by olfactory receptors. They have also been shown to have antimicrobial effects.

Olfactotropic

A pathogen that is capable of infecting cells within the olfactory mucosa.

Presbyosmia

An age-associated loss of smell.

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Wellford, S.A., Moseman, E.A. Olfactory immunology: the missing piece in airway and CNS defence. Nat Rev Immunol (2023). https://doi.org/10.1038/s41577-023-00972-9

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