title: Mouse hepatitis virus pathogenesis in the central nervous system is independent of IL-15 and natural killer cells.
abstract: Infection by the neurotropic JHM strain of mouse hepatitis virus (JHMV) results in an acute encephalomyelitis associated with demyelination. T cells are critical in controlling viral replication, but also contribute to central nervous system (CNS) pathogenesis. To reveal a role for innate effectors in anti-viral immunity and neurological disease, JHMV pathogenesis was studied in mice deficient in interleukin-15 (IL-15-/-) and natural killer (NK) cells. Clinical disease, CNS inflammation and demyelination in infected IL-15-/- mice were similar to wild-type mice. Despite the absence of NK cells and suboptimal CD8+ T cell responses, IL-15-/- mice controlled JHMV replication as efficiently as wild-type mice. Similar kinetics of class I and class II upregulation on microglia further suggested no role of NK cells in regulating major histocompatibility complex (MHC) molecule expression on resident CNS cells. IL-15 and NK cells thus appear dispensable for anti-viral immunity and CNS pathogenesis during acute JHMV infection.
authors.affiliation: Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zuo
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Stohlman
authors.forename: Jason B
authors.initials: JB
authors.lastname: Hoskin
authors.forename: David R
authors.initials: DR
authors.lastname: Hinton
authors.forename: Roscoe
authors.initials: R
authors.lastname: Atkinson
authors.forename: Cornelia C
authors.initials: CC
authors.lastname: Bergmann
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002490:Central Nervous System / Q000473:pathology* / Q000821:virology*; D018352:Coronavirus Infections / Q000276:immunology / Q000821:virology; D004679:Encephalomyelitis / Q000276:immunology / Q000821:virology; D005786:Gene Expression Regulation; D019409:Interleukin-15 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000378:metabolism*; D008285:Major Histocompatibility Complex; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism; D006517:Murine hepatitis virus / Q000472:pathogenicity*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism
chemical_list: D019409:Interleukin-15; D016692:Receptors, Antigen, T-Cell, gamma-delta