title: Dynamic change in natural killer cell type in the human ocular mucosa in situ as means of immune evasion by adenovirus infection.
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.
authors.affiliation: Singapore Eye Research Institute, Singapore, Singapore.|Duke-NUS Graduate Medical School, Clinical Sciences, Singapore, Singapore.|Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
authors.forename: N
authors.initials: N
authors.lastname: Yawata
authors.affiliation: Singapore Eye Research Institute, Singapore, Singapore.
authors.forename: K J
authors.initials: KJ
authors.lastname: Selva
authors.affiliation: Singapore Eye Research Institute, Singapore, Singapore.|Singapore National Eye Centre, Singapore, Singapore.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Liu
authors.affiliation: Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
authors.forename: K P
authors.initials: KP
authors.lastname: Tan
authors.affiliation: Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
authors.forename: A W L
authors.initials: AW
authors.lastname: Lee
authors.affiliation: Singapore Eye Research Institute, Singapore, Singapore.|Singapore National Eye Centre, Singapore, Singapore.
authors.forename: J
authors.initials: J
authors.lastname: Siak
authors.affiliation: Singapore Eye Research Institute, Singapore, Singapore.
authors.forename: W
authors.initials: W
authors.lastname: Lan
authors.affiliation: Singapore Eye Research Institute, Singapore, Singapore.
authors.forename: M
authors.initials: M
authors.lastname: Vania
authors.affiliation: Singapore National Eye Centre, Singapore, Singapore.
authors.forename: A
authors.initials: A
authors.lastname: Arundhati
authors.affiliation: Singapore Eye Research Institute, Singapore, Singapore.|Duke-NUS Graduate Medical School, Clinical Sciences, Singapore, Singapore.|Singapore National Eye Centre, Singapore, Singapore.|Department of Ophthalmology, Yong Loon Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: L
authors.initials: L
authors.lastname: Tong
authors.affiliation: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Singapore Eye Research Institute, Singapore, Singapore.|Duke-NUS Graduate Medical School, Clinical Sciences, Singapore, Singapore.|Singapore National Eye Centre, Singapore, Singapore.|Department of Ophthalmology, Yong Loon Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: J S
authors.initials: JS
authors.lastname: Mehta
authors.affiliation: Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.|Department of Pediatrics, Yong Loon Lin School of Medicine, National University of Singapore, Singapore, Singapore.|National University Health System, Singapore, Singapore.
authors.forename: M
authors.initials: M
authors.lastname: Yawata
mesh_terms: D000256:Adenoviridae / Q000276:immunology / Q000472:pathogenicity; D000257:Adenoviridae Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology; D019002:CD56 Antigen / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D018925:Chemokines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D018920:Coculture Techniques; D003228:Conjunctiva / Q000276:immunology* / Q000473:pathology / Q000821:virology; D003236:Conjunctivitis, Viral / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000821:virology; D005786:Gene Expression Regulation; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D006801:Humans; D057131:Immune Evasion; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000473:pathology / Q000821:virology; D009092:Mucous Membrane / Q000276:immunology* / Q000473:pathology / Q000821:virology; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000235:genetics / Q000276:immunology; D061251:Primary Cell Culture; D012720:Severity of Illness Index; D015398:Signal Transduction; D013666:Tears / Q000737:chemistry; D000097625:HLA-E Antigens
chemical_list: D019002:CD56 Antigen; D018925:Chemokines; D015395:Histocompatibility Antigens Class I; D055654:NK Cell Lectin-Like Receptor Subfamily C; D000097625:HLA-E Antigens; C527054:KLRC1 protein, human; C522918:NCAM1 protein, human