Herpes Simplex Virus type 1 infects Langerhans cells and the novel epidermal dendritic cell, Epi-cDC2s, via different entry pathways

Autor: Monica Miranda-Saksena, Ellis Patrick, Jake W. Rhodes, Kevin Danastas, Kirstie M. Bertram, Kerrie J Sandgren, Hafsa Rana, Naomi R. Truong, Min Kim, Steven Merten, Konrad L. Feng, Andrew N. Harman, Jake Lim, Ralph C. Cohen, Jason J. Herbert, Anthony L. Cunningham, Jacinta B. Smith
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Cultured tumor cells
Apoptosis
Herpesvirus 1
Human
Pathology and Laboratory Medicine
medicine.disease_cause
White Blood Cells
Spectrum Analysis Techniques
0302 clinical medicine
Animal Cells
Chlorocebus aethiops
Medicine and Health Sciences
HaCaT Cells
Biology (General)
Child
Cells
Cultured
Skin
0303 health sciences
education.field_of_study
Cell Death
integumentary system
T Cells
Dermis
Flow Cytometry
Cell biology
Cell Processes
Spectrophotometry
Medical Microbiology
Viral Pathogens
Child
Preschool
Viruses
Herpes Simplex Virus-1
Cell lines
Cytophotometry
Anatomy
Integumentary System
Cellular Types
Pathogens
Biological cultures
Research Article
Signal Transduction
Herpesviruses
Cell type
Adolescent
QH301-705.5
Immune Cells
Immunology
Population
Biology
Research and Analysis Methods
Microbiology
03 medical and health sciences
Immune system
Virology
Genetics
medicine
Animals
Humans
HeLa cells
education
Microbial Pathogens
Vero Cells
Molecular Biology
030304 developmental biology
Blood Cells
Epidermis (botany)
Organisms
Biology and Life Sciences
Infant
Herpes Simplex
Cell Biology
Dendritic cell
Virus Internalization
RC581-607
Cell cultures
Herpes Simplex Virus
Herpes simplex virus
Langerhans Cells
Vero cell
Parasitology
Epidermis
Immunologic diseases. Allergy
DNA viruses
030215 immunology
Zdroj: PLoS Pathogens, Vol 17, Iss 4, p e1009536 (2021)
PLoS Pathogens
ISSN: 1553-7374
1553-7366
Popis: Skin mononuclear phagocytes (MNPs) provide the first interactions of invading viruses with the immune system. In addition to Langerhans cells (LCs), we recently described a second epidermal MNP population, Epi-cDC2s, in human anogenital epidermis that is closely related to dermal conventional dendritic cells type 2 (cDC2) and can be preferentially infected by HIV. Here we show that in epidermal explants topically infected with herpes simplex virus (HSV-1), both LCs and Epi-cDC2s interact with HSV-1 particles and infected keratinocytes. Isolated Epi-cDC2s support higher levels of infection than LCs in vitro, inhibited by acyclovir, but both MNP subtypes express similar levels of the HSV entry receptors nectin-1 and HVEM, and show similar levels of initial uptake. Using inhibitors of endosomal acidification, actin and cholesterol, we found that HSV-1 utilises different entry pathways in each cell type. HSV-1 predominantly infects LCs, and monocyte-derived MNPs, via a pH-dependent pathway. In contrast, Epi-cDC2s are mainly infected via a pH-independent pathway which may contribute to the enhanced infection of Epi-cDC2s. Both cells underwent apoptosis suggesting that Epi-cDC2s may follow the same dermal migration and uptake by dermal MNPs that we have previously shown for LCs. Thus, we hypothesize that the uptake of HSV and infection of Epi-cDC2s will stimulate immune responses via a different pathway to LCs, which in future may help guide HSV vaccine development and adjuvant targeting.
Author summary Here we describe the first interactions of herpes simplex virus type 1 (HSV-1) with the human immune system as it enters the human genital skin. It was previously thought that this initial interaction of HSV-1 was only with ‘Langerhans cells’ (LCs) but we describe another important interaction with a new immune cell, Epi-cDC2s, which can also be infected by HIV and much more efficiently than LCs. Thus, there are now two of these types of immune cells resident in human epidermis. Therefore the way in which sexually transmitted and skin infecting viruses establish infection needs to be re-examined, including for HSV. We compared how these two cell types interacted with HSV-1 and showed Epi-cDC2s are more susceptible to HSV-1 infection than LCs and take up the virus via a different entry pathway. We speculate these cells may then carry HSV fragments to the dermis and then to lymph nodes to stimulate a protective immune response. These findings suggest similar routes may apply for chickenpox and cowpox viruses which also enter via the skin. Studying this pathway to establishment of natural immunity to HSV, may help guide the development of a successful vaccine.
Databáze: OpenAIRE
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