Identification of Genes Encoding Antimicrobial Proteins in Langerhans Cells

^{Division of Dermatology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, United States}

^{Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, United States}

^{Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, United States}

^{Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States}

^{Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, NSW, Australia}

^{School of Medical Sciences, Faculty of Medicine and Health Sydney, The University of Sydney, Westmead, NSW, Australia}

Edited by: Fatima Conceição-Silva, Oswaldo Cruz Foundation, Brazil

Reviewed by: Patrick M. Brunner, Medical University of Vienna, Austria; Yingping Xu, Southern Medical University, China; Marta Ewa Polak, University of Southampton, United Kingdom

*Correspondence: Robert L. Modlin, ude.alcu.tendem@nildomr

This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology

Edited by: Fatima Conceição-Silva, Oswaldo Cruz Foundation, Brazil

Reviewed by: Patrick M. Brunner, Medical University of Vienna, Austria; Yingping Xu, Southern Medical University, China; Marta Ewa Polak, University of Southampton, United Kingdom

Received 2021 Apr 14; Accepted 2021 Aug 6.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Abstract

Langerhans cells (LCs) reside in the epidermis where they are poised to mount an antimicrobial response against microbial pathogens invading from the outside environment. To elucidate potential pathways by which LCs contribute to host defense, we mined published LC transcriptomes deposited in GEO and the scientific literature for genes that participate in antimicrobial responses. Overall, we identified 31 genes in LCs that encode proteins that contribute to antimicrobial activity, ten of which were cross-validated in at least two separate experiments. Seven of these ten antimicrobial genes encode chemokines, CCL1, CCL17, CCL19, CCL2, CCL22, CXCL14 and CXCL2, which mediate both antimicrobial and inflammatory responses. Of these, CCL22 was detected in seven of nine transcriptomes and by PCR in cultured LCs. Overall, the antimicrobial genes identified in LCs encode proteins with broad antibacterial activity, including against Staphylococcus aureus, which is the leading cause of skin infections. Thus, this study illustrates that LCs, consistent with their anatomical location, are programmed to mount an antimicrobial response against invading pathogens in skin.

Keywords: Langerhans cells, dendritic cells, antimicrobial peptides, immunity, skin, transcriptome, bioinformatics

Abstract

By mining publicly available data in GEO DataSets, we were able to identify 23 genes encoding antimicrobial peptides that are more strongly expressed in LCs vs. other DC subtypes and/or in LCs activated with cytokines vs. LCs with no activation. N/A, Not applicable.

Click here for additional data file.^{(2.7M, docx)}

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