title: Interferon γ-dependent migration of microglial cells in the retina after systemic cytomegalovirus infection.
abstract: Microglial cells are the resident macrophages of the central nervous system and participate in both innate and adaptive immune responses but can also lead to exacerbation of neurodegenerative pathologies after viral infections. Microglia in the outer layers of the retina and the subretinal space are thought to be involved in retinal diseases where low-grade chronic inflammation and oxidative stress play a role. This study investigated the effect of systemic infection with murine cytomegalovirus on the distribution and dynamics of retinal microglia cells. Systemic infection with murine cytomegalovirus elicited a significant increase in the number of microglia in the subretinal space and an accumulation of iris macrophages, along with morphological signs of activation. Interferon γ (IFN-γ)-deficient mice failed to induce changes in microglia distribution. Bone marrow chimera experiments confirmed that microglial cells in the subretinal space were not recruited from the circulating monocyte pool, but rather represented an accumulation of resident microglial cells from within the retina. Our results demonstrate that a systemic viral infection can lead to IFN-γ-mediated accumulation of microglia into the outer retinal layers and offer proof of concept that systemic viral infections alter the ocular microenvironment and therefore, may influence the course of diseases such as macular degeneration, diabetic retinopathy, or autoimmune uveitis, where low-grade inflammation is implicated.
authors: Ocular Immunology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Australia.
authors: Martin S
authors: MS
authors: Zinkernagel
authors: Holly R
authors: HR
authors: Chinnery
authors: Monique L
authors: ML
authors: Ong
authors: Claire
authors: C
authors: Petitjean
authors: Valentina
authors: V
authors: Voigt
authors: Samuel
authors: S
authors: McLenachan
authors: Paul G
authors: PG
authors: McMenamin
authors: Geoffrey R
authors: GR
authors: Hill
authors: John V
authors: JV
authors: Forrester
authors: Matthew E
authors: ME
authors: Wikstrom
authors: Mariapia A
authors: MA
authors: Degli-Esposti
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D003586:Cytomegalovirus Infections / Q000473:pathology* / Q000821:virology; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000378:metabolism*; D007498:Iris / Q000473:pathology / Q000821:virology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000473:pathology* / Q000821:virology; D018146:Muromegalovirus / Q000187:drug effects / Q000502:physiology*; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000494:pharmacology; D012160:Retina / Q000187:drug effects / Q000473:pathology* / Q000821:virology*; D055214:Retinal Photoreceptor Cell Outer Segment / Q000187:drug effects / Q000473:pathology / Q000821:virology
chemical_list: C491049:Aif1 protein, mouse; C408982:CPG-oligonucleotide; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D053594:Myeloid Differentiation Factor 88; D009838:Oligodeoxyribonucleotides; D007371:Interferon-gamma