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The influence of skin microorganisms on cutaneous immunity

Key Points

  • The skin is a complex and dynamic ecosystem inhabited by many microorganisms.

  • The capacity of a given microorganism to trigger or promote disease is dependent on the state of immune activation of the host, the host's genetic predisposition and/or microorganism localization.

  • The skin microbiota can promote both innate and adaptive immunity to skin pathogens.

  • In many settings, optimal skin immunity is induced through networks of antigen-presenting cell subsets.

  • The skin is a large reservoir of tissue-resident memory T cells that can have an important role in protective immunity against pathogens.

  • Skin immune disorders in humans are associated with the enrichment of defined species of microorganisms.

Abstract

The skin is a complex and dynamic ecosystem that is inhabited by many microorganisms. Recent evidence highlights the profound reliance of the skin immune system on its resident microbiota for both host defence and tissue repair. This tissue is also a primary target for infections, which are in some cases caused by normal constituents of the microbiota. In the context of infections and genetic predispositions that are associated with barrier or regulatory network defects, microorganism-induced inflammatory cycles can contribute to the initiation and/or amplification of skin disorders. This Review will discuss some of our current understanding of skin–microbiota and skin–pathogen interactions in the context of homeostasis and diseases and highlight current gaps in our understanding of the skin immune ecosystem.

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Figure 1: Contextuality of pathogenesis.
Figure 2: Structure and cellular components of the skin and control of immunity by skin-resident microorganisms.
Figure 3: Role of skin-resident dendritic cells in the induction of T cell responses to skin microorganisms.
Figure 4: Host–microorganism inflammatory circles: microorganisms can contribute to the initiation and amplification of inflammatory loops within the skin compartment.

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Acknowledgements

The authors apologize to their colleagues for not having cited all papers relevant to this expanding field of research (and in particular older literature) because of space constraints and strict editorial limitation for reference number. This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases. S. T. was supported by an EMBO fellowship. The authors thank all members of the Belkaid laboratory for discussion and more particularly N. Bouladoux and J. Kehr for their editorial help with the manuscript.

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Glossary

Mutualism

The relationship between two different species that live in close proximity and benefit from one another.

Parasitism

The relationship between two different species that live in close proximity, in which one species (the parasite) benefits at the expense of the other (the host).

Commensalism

The relationship between two different species, in which one species benefits from the other without affecting it.

Antimicrobial peptides

(AMPs). Molecules that can rapidly kill or inactivate a diverse range of microorganisms, including Gram-negative and Gram-positive bacteria, fungi, viruses and parasites.

Sebaceous glands

Small glands in the skin that secrete an oily matter (sebum) into the hair follicles to lubricate the skin and hair.

Lipoteichoic acid

A major component of the cell wall of Gram-positive bacteria such as Staphylococcus epidermidis.

Filaggrin

A filament-associated protein that binds to keratin fibres in epithelial cells and is important for maturation of skin epithelial cells into the corneocytes that form the outermost protective layer of human skin.

Nociceptors

Sensory receptors on nerve cells that respond to potentially damaging stimuli by sending signals to the spinal cord and brain.

Concomitant immunity

A paradoxical immune status in which resistance to reinfection coincides with the persistence of the original infection.

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Belkaid, Y., Tamoutounour, S. The influence of skin microorganisms on cutaneous immunity. Nat Rev Immunol 16, 353–366 (2016). https://doi.org/10.1038/nri.2016.48

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