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Human Three-Dimensional Models for Studying Skin Pathogens

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Three Dimensional Human Organotypic Models for Biomedical Research

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 430))

Abstract

Skin is the most exposed surface of the human body, separating the microbe-rich external environment, from the sterile inner part. When skin is breached or its homeostasis is perturbed, bacterial, fungal and viral pathogens can cause local infections or use the skin as an entry site to spread to other organs. In the last decades, it has become clear that skin provides niches for permanent microbial colonization, and it actively interacts with microorganisms. This crosstalk promotes skin homeostasis and immune maturation, preventing expansion of harmful organisms. Skin commensals, however, are often found to be skin most prevalent and dangerous pathogens. Despite the medical interest, mechanisms of colonization and invasion for most skin pathogens are poorly understood. This limitation is due to the lack of reliable skin models. Indeed, animal models do not adequately mimic neither the anatomy nor the immune response of human skin. Human 3D skin models overcome these limitations and can provide new insights into the molecular mechanisms of microbial pathogenesis. Herein, we address the strengths and weaknesses of different types of human skin models and we review the main findings obtained using these models to study skin pathogens.

Elena Boero and Malgorzata Ewa Mnich—These authors contributed equally to the work.

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Abbreviations

AD:

Atopic dermatitis

APC:

Antigen-presenting cell

cDC:

Conventional DC

CHIPS:

Chemotaxis inhibitory protein of Staphylococcus aureus

CLA:

Cutaneous lymphocyte antigen

ClfA:

Clumping factor A

ClfB:

Clumping factor B

DC:

Dendritic cell

GAS:

Group A Streptococcus

GFP:

Green fluorescent protein

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

GvH:

Graft-versus-host

GvHD:

Graft-versus-host disease

HIV:

Human immunodeficiency virus

HPV:

Human papillomavirus

HSE:

Human skin equivalent

HSV:

Herpes simplex virus

IFN:

Interferon

IL:

Interleukin

LC:

Langerhans cell

MCPyV:

Merkel cell polyomavirus

moDC:

Monocyte-derived DC

NSTI:

Necrotizing soft tissue infection

PBMCs:

Peripheral blood mononuclear cells

PIA:

Polysaccharide intracellular adhesin

PSMα:

Phenol-soluble modulins α

PVL:

Panton–Valentine leukocidin

ROS:

Reactive oxygen species

SCIN:

Staphylococcal complement inhibitor

SEA:

Staphylococcal enterotoxin A

SEB:

Staphylococcal enterotoxin B

SLS:

Streptolysin S

SLO:

Streptolysin O

SSI:

Surgical site infection

SSS:

Scalded skin syndrome

SSTI:

Skin and soft tissues infection

TEff:

Effector T cell

TEM:

Effector memory T cell

TRM:

Tissue-resident memory T cells

TLR2:

Toll-like receptor 2

TNFα:

Tumour necrosis factor α

VZV:

Varicella zoster virus

WGS:

Whole genome shotgun

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Competing Interests

Elena Boero (EB) and Malgorzata Ewa Mnich are participating in a postgraduate studentship programme (DISSection) at GSK. Andrea Guido Oreste Manetti, Elisabetta Soldaini and Fabio Bagnoli are employees of GSK. Fabio Bagnoli reports ownership of GSK stocks and owns patents on S. aureus vaccine candidates. Luca Grimaldi is an employee of the University of Siena, Italy, and previously was involved in a collaboration between GSK and the Azienda Ospedaliera Universitaria Senese, Siena, Italy, providing human samples for research work conducted in GSK. The study was approved by local ethical committees and conducted according to good clinical practice in accordance with the declaration of Helsinki. Patients had given their written consent to the study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript, apart from those disclosed.

Funding

This work was undertaken at the request of and sponsored by GlaxoSmithKline Biologicals SA, and it was also supported by the European Union’s Horizon 2020 research H2020-MSCA-ITN (No. 675106 coordinated by Dr. Fabio Bagnoli, GSK, Siena, Italy).

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Authors and Affiliations

  1. GSK, Siena, Italy

    Elena Boero, Malgorzata Ewa Mnich, Andrea Guido Oreste Manetti, Elisabetta Soldaini & Fabio Bagnoli

  2. Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy

    Luca Grimaldi

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  1. Elena Boero
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  2. Malgorzata Ewa Mnich
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  3. Andrea Guido Oreste Manetti
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  4. Elisabetta Soldaini
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  5. Luca Grimaldi
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  6. Fabio Bagnoli
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Corresponding author

Correspondence to Fabio Bagnoli .

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  1. GSK Vaccines Research, Siena, Italy

    Fabio Bagnoli

  2. GSK Vaccines Research, Siena, Italy

    Rino Rappuoli

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Boero, E., Mnich, M.E., Manetti, A.G.O., Soldaini, E., Grimaldi, L., Bagnoli, F. (2021). Human Three-Dimensional Models for Studying Skin Pathogens. In: Bagnoli, F., Rappuoli, R. (eds) Three Dimensional Human Organotypic Models for Biomedical Research. Current Topics in Microbiology and Immunology, vol 430. Springer, Cham. https://doi.org/10.1007/82_2020_219

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