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.

Kinetics of Tear Fluid Proteins after Endothelial Keratoplasty and Predictive Factors for Recovery from Corneal Haze

“…Tear fluid from both the transplant and non-transplant eyes was collected at the same time. Tear fluid collection used Schirmer strip filter paper as described previously [16]. Clinical records were collected with the following information: status of corneal epithelial defect, conjunctival congestion, conditions of corneal stromal haze [Fantes grading; scored from 0 to 4; none (0), minimal (1), mild (2), moderate (3), and severe (4)], inflammation status in the anterior chamber, and LogMAR visual acuity.…”

NK cell recruitment in salivary glands provides early viral control but is dispensable for tertiary lymphoid structure formation

“…The control of viral infections is a hallmark of NK cell effector‐functions as shown in vivo in several animal models infected with herpes simplex‐1, influenza or murine cytomegalovirus (MCMV) . Several viruses have developed escape mechanisms that interfere with NK cell homeostasis, phenotype, and effector functions . Salivary glands (SGs) represent a permissive site for the persistence of many viruses including CMV, Epstein‐Barr virus (EBV), and Hepatitis C virus (HCV) .…”

“…6,7 Several viruses have developed escape mechanisms that interfere with NK cell homeostasis, phenotype, and effector functions. 8 Salivary glands (SGs) represent a permissive site for the persistence of many viruses including CMV, 9 Epstein-Barr virus (EBV), 10 and Hepatitis C virus (HCV). 11 This phenomenon has been associated with a higher incidence of Sjögren's syndrome (SS), an autoimmune disease characterized by immune cell infiltration in the SGs organized in tertiary lymphoid structures (TLS) and leading to exocrine dysfunction.…”

Evaluation of the Effect of the Ophthalmic Remedies Combination on the Viability of Human Conjunctival Cell Culture Chang Conjunctiva

“…Эти колориметрические методы важны для оценки токсичности и потенциальной опасности лекарственных веществ в условиях in vivo, и в частности, для определения предварительных нетоксических концентраций с целью дальнейшего применения у лабораторных животных на следующем этапе доклинических испытаний. В качестве материала принято использовать различные клеточные линии, содержащие клетки роговицы (эпителий, эндотелий) и конъюнктивы (эпителий, фибробласты, бокаловидные клетки) [1,2,3,4].…”

“…Весьма ограниченное количество работ посвящено изучению местных цитокиновых реакций и эффектов воздействия готовых глазных капель (и их комбинаций) на клеточные культуры, в частности, при вирусных инфекциях глаз; нами обнаружены единичные работы с использованием подобных методик [1,21]. На наш взгляд, недостаточно внимания в отечественной литературе уделяется развитию научно-обоснованных подходов к терапии воспалительных заболеваний глаз вирусной природы с использованием общепринятых фундаментальных биологических методов, тогда как обилие готовых лекарственных форм создает условия для развития полипрагмазии и лекарственной аллергии в офтальмологии [22,23,24].…”