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J Proteomics. 2020 Mar 30;216:103670. doi: 10.1016/j.jprot.2020.103670. Epub 2020 Jan 25.

Mechanisms of innate events during skin reaction following intradermal injection of seasonal influenza vaccine.

Author information

1
Sorbonne Université, Centre d'Immunologie et des Maladies Infectieuses - Paris (Cimi-Paris), INSERM U1135, Paris, France.
2
Univ. Lille, INSERM, CHU Lille, U1008 - Controlled Drug Delivery Systems and Biomaterials, F-59000 Lille, France; ImaBiotech, 152 rue du Docteur Yersin, 59120 Loos, France.
3
Univ. Lille, Inserm, U1192 - Protéomique, Réponse Inflammatoire et Spectrométrie de Masse-PRISM, F-59000 Lille, France.
4
Sorbonne Université, Centre d'Immunologie et des Maladies Infectieuses - Paris (Cimi-Paris), INSERM U1135, Paris, France; Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin (2), 10117 Berlin, Germany.
5
CEA - Université Paris Sud 11 - INSERM U1184, Immunology of Viral Infections and Autoimmune Diseases, Institut de Biologie François Jacob, 92265 Fontenay-aux-Roses, France.
6
Sorbonne Université, Centre d'Immunologie et des Maladies Infectieuses - Paris (Cimi-Paris), INSERM U1135, Paris, France; Service de Dermatologie et d'Allergologie, Hôpital Tenon, 4 rue de la Chine, Hôpitaux Universitaire Est Parisien (HUEP), Assistance Publique Hôpitaux de Paris (APHP), 75020 Paris, France.
7
Sorbonne Université, Centre d'Immunologie et des Maladies Infectieuses - Paris (Cimi-Paris), INSERM U1135, Paris, France; Service de chirurgie plastique reconstructrice, esthétique, centre des brûlés, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris (APHP), 1 avenue Claude Vellefaux, 75010 Paris, France.
8
ImaBiotech, 152 rue du Docteur Yersin, 59120 Loos, France.
9
Sorbonne Université, Centre d'Immunologie et des Maladies Infectieuses - Paris (Cimi-Paris), INSERM U1135, Paris, France. Electronic address: behazine.combadiere@inserm.fr.

Abstract

The skin plays a crucial role in host defences against microbial attack and the innate cells must provide the immune system with sufficient information to organize these defences. This unique feature makes the skin a promising site for vaccine administration. Although cellular innate immune events during vaccination have been widely studied, initial events remain poorly understood. Our aim is to determine molecular biomarkers of skin innate reaction after intradermal (i.d.) immunization. Using an ex vivo human explant model from healthy donors, we investigated by NanoLC-MS/MS analysis and MALDI-MSI imaging, to detect innate molecular events (lipids, metabolites, proteins) few hours after i.d. administration of seasonal trivalent influenza vaccine (TIV). This multimodel approach allowed to identify early molecules differentially expressed in dermal and epidermal layers at 4 and 18 h after TIV immunization compared with control PBS. In the dermis, the most relevant network of proteins upregulated were related to cell-to-cell signalling and cell trafficking. The molecular signatures detected were associated with chemokines such as CXCL8, a chemoattractant of neutrophils. In the epidermis, the most relevant networks were associated with activation of antigen-presenting cells and related to CXCL10. Our study proposes a novel step-forward approach to identify biomarkers of skin innate reaction. SIGNIFICANCE: To our knowledge, there is no study analyzing innate molecular reaction to vaccines at the site of skin immunization. What is known on skin reaction is based on macroscopic (erythema, redness…), microscopic (epidermal and dermal tissues) and cellular events (inflammatory cell infiltrate). Therefore, we propose a multimodal approach to analyze molecular events at the site of vaccine injection on skin tissue. We identified early molecular networks involved biological functions such cell migration, cell-to-cell interaction and antigen presentation, validated by chemokine expression, in the epidermis and dermis, then could be used as early indicator of success in immunization.

KEYWORDS:

Biomarkers; Innate immunity; Intradermal vaccination; Mass spectrometry; Skin

PMID:
31991189
DOI:
10.1016/j.jprot.2020.103670
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Conflict of interest statement

Declaration of Competing Interest The authors have no financial conflicts of interest.

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