title: The bacteriostatic protein lipocalin 2 is induced in the central nervous system of mice with west Nile virus encephalitis.
abstract: Lipocalin 2 (Lcn2) is a bacteriostatic factor produced during the innate immune response to bacterial infection. Whether Lcn2 has a function in viral infection is unknown. We investigated the regulation and function of Lcn2 in the central nervous system (CNS) of mice during West Nile virus (WNV) encephalitis. Lcn2 mRNA and protein were induced in the brain by day 5, and this induction increased further by day 7 postinfection but was delayed compared with the induction of the toll-like receptor 3 (TLR3) gene, retinoic acid-inducible gene 1 (RIG-I), and melanoma differentiation-associated protein 5 (MDA5) gene. The Lcn2 mRNA and protein were both found at high levels in the choroid plexus, vascular endothelium, macrophage/microglia, and astrocytes. However, some neuronal subsets contained Lcn2 protein but no detectable mRNA. In Lcn2 knockout (KO) mice, with the exception of CXC motif chemokine 5 (CXCL5), which was significantly more downregulated than in wild-type (WT) mice, expression levels of a number of other host response genes were similar in the two genotypes. The brain from Lcn2 and WT mice with WNV encephalitis contained similar numbers of infiltrating macrophages, granulocytes, and T cells. Lcn2 KO and WT mice had no significant difference in tissue viral loads or survival after infection with different doses of WNV. We conclude that Lcn2 gene expression is induced to high levels in a time-dependent fashion in a variety of cells and regions of the CNS of mice with WNV encephalitis. The function of Lcn2 in the host response to WNV infection remains largely unknown, but our data indicate that it is dispensable as an antiviral or immunoregulatory factor in WNV encephalitis.
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, N.S.W., Australia.
authors.forename: Aline L
authors.initials: AL
authors.lastname: Noçon
authors.forename: Jacque P K
authors.initials: JP
authors.lastname: Ip
authors.forename: Rachael
authors.initials: R
authors.lastname: Terry
authors.forename: Sue Ling
authors.initials: SL
authors.lastname: Lim
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Getts
authors.forename: Marcus
authors.initials: M
authors.lastname: Müller
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Hofer
authors.forename: Nicholas J C
authors.initials: NJ
authors.lastname: King
authors.forename: Iain L
authors.initials: IL
authors.lastname: Campbell
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism*; D017403:In Situ Hybridization; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D015513:Oncogene Proteins / Q000378:metabolism*; D015854:Up-Regulation; D014901:West Nile Fever / Q000235:genetics / Q000378:metabolism*
chemical_list: D000209:Acute-Phase Proteins; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; C071332:Lcn2 protein, mouse