title: Type 1 Interferons and NK Cells Limit Murine Cytomegalovirus Escape from the Lymph Node Subcapsular Sinus.
abstract: Cytomegaloviruses (CMVs) establish chronic, systemic infections. Peripheral infection spreads via lymph nodes, which are also a focus of host defence. Thus, this is a point at which systemic infection spread might be restricted. Subcapsular sinus macrophages (SSM) captured murine CMV (MCMV) from the afferent lymph and poorly supported its replication. Blocking the type I interferon (IFN-I) receptor (IFNAR) increased MCMV infection of SSM and of the fibroblastic reticular cells (FRC) lining the subcapsular sinus, and accelerated viral spread to the spleen. Little splenic virus derived from SSM, arguing that they mainly induce an anti-viral state in the otherwise susceptible FRC. NK cells also limited infection, killing infected FRC and causing tissue damage. They acted independently of IFN-I, as IFNAR blockade increased NK cell recruitment, and NK cell depletion increased infection in IFNAR-blocked mice. Thus SSM restricted MCMV infection primarily though IFN-I, with NK cells providing a second line of defence. The capacity of innate immunity to restrict MCMV escape from the subcapsular sinus suggested that enhancing its recruitment might improve infection control.
authors.affiliation: School of Chemistry and Molecular Biosciences and Child Health Research Centre, University of Queensland, Brisbane, Australia.
authors.forename: Helen E
authors.identifier: http://orcid.org/0000-0002-7214-2767
authors.initials: HE
authors.lastname: Farrell
authors.affiliation: School of Chemistry and Molecular Biosciences and Child Health Research Centre, University of Queensland, Brisbane, Australia.
authors.forename: Kimberley
authors.initials: K
authors.lastname: Bruce
authors.affiliation: School of Chemistry and Molecular Biosciences and Child Health Research Centre, University of Queensland, Brisbane, Australia.
authors.forename: Clara
authors.initials: C
authors.lastname: Lawler
authors.affiliation: Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, United States of America.
authors.forename: Rhonda D
authors.initials: RD
authors.lastname: Cardin
authors.affiliation: Child Health Research Centre, University of Queensland, Brisbane, Australia.
authors.forename: Nicholas J
authors.identifier: http://orcid.org/0000-0001-7368-1925
authors.initials: NJ
authors.lastname: Davis-Poynter
authors.affiliation: School of Chemistry and Molecular Biosciences and Child Health Research Centre, University of Queensland, Brisbane, Australia.
authors.forename: Philip G
authors.identifier: http://orcid.org/0000-0002-3520-5060
authors.initials: PG
authors.lastname: Stevenson
mesh_terms: D000818:Animals; D006566:Herpesviridae Infections / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D007370:Interferon Type I / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology* / Q000821:virology; D008264:Macrophages / Q000821:virology; D051379:Mice; D018146:Muromegalovirus / Q000276:immunology
chemical_list: D007370:Interferon Type I