altered monocyte and langerhans cell innate immunity in patients with recurrent respiratory papillomatosis (rrp)

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ID: 151895
2020
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Abstract
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 (TH2-/Treg) adaptive immunity in papillomas and blood, enriched immature Langerhans cell (iLC) numbers, and overexpression of cyclooxygenase-2/prostaglandin E2 (PGE2) 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 E2, 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 PGE2 exposure in vivo. The immunosuppressive papilloma microenvironment likely alters iLC responses, and vice versa, supporting TH2-like/Treg HPV-specific adaptive immunity in RRP.
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israr2020frontiersaltered Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Mohd Israr;James A. DeVoti;Fung Lam;Allan L. Abramson;Bettie M. Steinberg;Bettie M. Steinberg;Vincent R. Bonagura;Vincent R. Bonagura
Journal sudebno-meditsinskaia ekspertiza
Year 2020
DOI
10.3389/fimmu.2020.00336
URL
https://www.frontiersin.org/article/10.3389/fimmu.2020.00336/full
Keywords
innate immunity monocyte allergy

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