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.