Cargando…

Altered Monocyte and Langerhans Cell Innate Immunity in Patients With Recurrent Respiratory Papillomatosis (RRP)

The micromilieu within respiratory papillomas supports persistent human papillomavirus (HPV) infection and disease recurrence in patients with recurrent respiratory papillomatosis (RRP). These patients show polarized (T(H)2-/Treg) adaptive immunity in papillomas and blood, enriched immature Langerha...

Descripción completa

Detalles Bibliográficos
Autores principales: Israr, Mohd, DeVoti, James A., Lam, Fung, Abramson, Allan L., Steinberg, Bettie M., Bonagura, Vincent R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076114/
https://www.ncbi.nlm.nih.gov/pubmed/32210959
http://dx.doi.org/10.3389/fimmu.2020.00336
_version_ 1783507158936059904
author Israr, Mohd
DeVoti, James A.
Lam, Fung
Abramson, Allan L.
Steinberg, Bettie M.
Bonagura, Vincent R.
author_facet Israr, Mohd
DeVoti, James A.
Lam, Fung
Abramson, Allan L.
Steinberg, Bettie M.
Bonagura, Vincent R.
author_sort Israr, Mohd
collection PubMed
description The micromilieu within respiratory papillomas supports persistent human papillomavirus (HPV) infection and disease recurrence in patients with recurrent respiratory papillomatosis (RRP). These patients show polarized (T(H)2-/Treg) adaptive immunity in papillomas and blood, enriched immature Langerhans cell (iLC) numbers, and overexpression of cyclooxygenase-2/prostaglandin E(2) (PGE(2)) in the upper airway. Blood monocyte-derived, and tissue-derived iLCs from RRP patients and controls were now studied to more fully understand innate immune dysregulation in RRP. Patients' monocytes generated fewer iLCs than controls, due to a reduced fraction of classical monocytes that generated most but not all the iLCs. Prostaglandin E(2), which was elevated in RRP plasma, reduced monocyte-iLC differentiation from controls to the levels of RRP patients, but had no effect on subsequent iLC maturation. Cytokine/chemokine responses by iLCs from papillomas, foreskin, and abdominal skin differed significantly. Freshly derived tissue iLCs expressed low CCL-1 and high CCL-20 mRNAs and were unresponsive to IL-36γ stimulation. Papilloma iLCs uniquely expressed IL-36γ at baseline and expressed CCL1 when cultured overnight outside their immunosuppressive microenvironment without additional stimulation. We conclude that monocyte/iLC innate immunity is impaired in RRP, in part due to increased PGE(2) exposure in vivo. The immunosuppressive papilloma microenvironment likely alters iLC responses, and vice versa, supporting T(H)2-like/Treg HPV-specific adaptive immunity in RRP.
format Online
Article
Text
id pubmed-7076114
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-70761142020-03-24 Altered Monocyte and Langerhans Cell Innate Immunity in Patients With Recurrent Respiratory Papillomatosis (RRP) Israr, Mohd DeVoti, James A. Lam, Fung Abramson, Allan L. Steinberg, Bettie M. Bonagura, Vincent R. Front Immunol Immunology The micromilieu within respiratory papillomas supports persistent human papillomavirus (HPV) infection and disease recurrence in patients with recurrent respiratory papillomatosis (RRP). These patients show polarized (T(H)2-/Treg) adaptive immunity in papillomas and blood, enriched immature Langerhans cell (iLC) numbers, and overexpression of cyclooxygenase-2/prostaglandin E(2) (PGE(2)) in the upper airway. Blood monocyte-derived, and tissue-derived iLCs from RRP patients and controls were now studied to more fully understand innate immune dysregulation in RRP. Patients' monocytes generated fewer iLCs than controls, due to a reduced fraction of classical monocytes that generated most but not all the iLCs. Prostaglandin E(2), which was elevated in RRP plasma, reduced monocyte-iLC differentiation from controls to the levels of RRP patients, but had no effect on subsequent iLC maturation. Cytokine/chemokine responses by iLCs from papillomas, foreskin, and abdominal skin differed significantly. Freshly derived tissue iLCs expressed low CCL-1 and high CCL-20 mRNAs and were unresponsive to IL-36γ stimulation. Papilloma iLCs uniquely expressed IL-36γ at baseline and expressed CCL1 when cultured overnight outside their immunosuppressive microenvironment without additional stimulation. We conclude that monocyte/iLC innate immunity is impaired in RRP, in part due to increased PGE(2) exposure in vivo. The immunosuppressive papilloma microenvironment likely alters iLC responses, and vice versa, supporting T(H)2-like/Treg HPV-specific adaptive immunity in RRP. Frontiers Media S.A. 2020-03-10 /pmc/articles/PMC7076114/ /pubmed/32210959 http://dx.doi.org/10.3389/fimmu.2020.00336 Text en Copyright © 2020 Israr, DeVoti, Lam, Abramson, Steinberg and Bonagura. http://creativecommons.org/licenses/by/4.0/ 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.
spellingShingle Immunology
Israr, Mohd
DeVoti, James A.
Lam, Fung
Abramson, Allan L.
Steinberg, Bettie M.
Bonagura, Vincent R.
Altered Monocyte and Langerhans Cell Innate Immunity in Patients With Recurrent Respiratory Papillomatosis (RRP)
title Altered Monocyte and Langerhans Cell Innate Immunity in Patients With Recurrent Respiratory Papillomatosis (RRP)
title_full Altered Monocyte and Langerhans Cell Innate Immunity in Patients With Recurrent Respiratory Papillomatosis (RRP)
title_fullStr Altered Monocyte and Langerhans Cell Innate Immunity in Patients With Recurrent Respiratory Papillomatosis (RRP)
title_full_unstemmed Altered Monocyte and Langerhans Cell Innate Immunity in Patients With Recurrent Respiratory Papillomatosis (RRP)
title_short Altered Monocyte and Langerhans Cell Innate Immunity in Patients With Recurrent Respiratory Papillomatosis (RRP)
title_sort altered monocyte and langerhans cell innate immunity in patients with recurrent respiratory papillomatosis (rrp)
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076114/
https://www.ncbi.nlm.nih.gov/pubmed/32210959
http://dx.doi.org/10.3389/fimmu.2020.00336
work_keys_str_mv AT israrmohd alteredmonocyteandlangerhanscellinnateimmunityinpatientswithrecurrentrespiratorypapillomatosisrrp
AT devotijamesa alteredmonocyteandlangerhanscellinnateimmunityinpatientswithrecurrentrespiratorypapillomatosisrrp
AT lamfung alteredmonocyteandlangerhanscellinnateimmunityinpatientswithrecurrentrespiratorypapillomatosisrrp
AT abramsonallanl alteredmonocyteandlangerhanscellinnateimmunityinpatientswithrecurrentrespiratorypapillomatosisrrp
AT steinbergbettiem alteredmonocyteandlangerhanscellinnateimmunityinpatientswithrecurrentrespiratorypapillomatosisrrp
AT bonaguravincentr alteredmonocyteandlangerhanscellinnateimmunityinpatientswithrecurrentrespiratorypapillomatosisrrp