Dynamic change in natural killer cell type in the human ocular mucosa in situ as means of immune evasion by adenovirus infection

Nobuyo Yawata, K. J. Selva, Y. C. Liu, K. P. Tan, A. W.L. Lee, J. Siak, W. Lan, M. Vania, A. Arundhati, L. Tong, J. Li, J. S. Mehta, M. Yawata

Research output: Contribution to journalArticle

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Abstract

The most severe form of virus-induced inflammation at the ocular surface is epidemic keratoconjunctivitis (EKC), often caused by group D human adenoviruses (HAdVs). We investigated the dynamics and mechanisms of changes in natural killer (NK) cell types in the human ocular mucosal surface in situ over the course of infection. In the acute phase of infection, the mature CD56 dim NK cells that comprise a major subpopulation in the normal human conjunctiva are replaced by CD56 bright NK cells recruited to the ocular surface by chemokines produced by the infected epithelium, and NKG2A-expressing CD56 dim and CD56 bright NK cells become the major subpopulations in severe inflammation. These NK cells attracted to the mucosal surface are however incapable of mounting a strong antiviral response because of upregulation of the inhibitory ligand human leukocyte antigen-E (HLA-E) on infected epithelium. Furthermore, group D HAdVs downregulate ligands for activating NK cell receptors, thus rendering even the mature NKG2A - NK cells unresponsive, an immune-escape mechanism distinct from other adenoviruses. Our findings imply that the EKC-causing group D HAdVs utilize these multiple pathways to inhibit antiviral NK cell responses in the initial stages of the infection.

Original languageEnglish
Pages (from-to)159-170
Number of pages12
JournalMucosal Immunology
Volume9
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

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Adenoviridae Infections
Immune Evasion
Natural Killer Cells
Mucous Membrane
Human Adenoviruses
Keratoconjunctivitis
Antiviral Agents
Epithelium
Infection
Natural Killer Cell Receptors
Ligands
Inflammation
Conjunctiva
HLA Antigens
Chemokines
Adenoviridae
Up-Regulation
Down-Regulation
Viruses

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Dynamic change in natural killer cell type in the human ocular mucosa in situ as means of immune evasion by adenovirus infection. / Yawata, Nobuyo; Selva, K. J.; Liu, Y. C.; Tan, K. P.; Lee, A. W.L.; Siak, J.; Lan, W.; Vania, M.; Arundhati, A.; Tong, L.; Li, J.; Mehta, J. S.; Yawata, M.

In: Mucosal Immunology, Vol. 9, No. 1, 01.01.2016, p. 159-170.

Research output: Contribution to journalArticle

Yawata, N, Selva, KJ, Liu, YC, Tan, KP, Lee, AWL, Siak, J, Lan, W, Vania, M, Arundhati, A, Tong, L, Li, J, Mehta, JS & Yawata, M 2016, 'Dynamic change in natural killer cell type in the human ocular mucosa in situ as means of immune evasion by adenovirus infection', Mucosal Immunology, vol. 9, no. 1, pp. 159-170. https://doi.org/10.1038/mi.2015.47
Yawata, Nobuyo ; Selva, K. J. ; Liu, Y. C. ; Tan, K. P. ; Lee, A. W.L. ; Siak, J. ; Lan, W. ; Vania, M. ; Arundhati, A. ; Tong, L. ; Li, J. ; Mehta, J. S. ; Yawata, M. / Dynamic change in natural killer cell type in the human ocular mucosa in situ as means of immune evasion by adenovirus infection. In: Mucosal Immunology. 2016 ; Vol. 9, No. 1. pp. 159-170.
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