Type 1 interferons and NK cells limit murine cytomegalovirus escape from the lymph node subcapsular sinus

Farrell, Helen E., Bruce, Kimberley, Lawler, Clara, Cardin, Rhonda D., Davis-Poynter, Nicholas J. and Stevenson, Philip G. (2016) Type 1 interferons and NK cells limit murine cytomegalovirus escape from the lymph node subcapsular sinus. PLoS Pathogens, 12 12: e1006069. doi:10.1371/journal.ppat.1006069

Author Farrell, Helen E.
Bruce, Kimberley
Lawler, Clara
Cardin, Rhonda D.
Davis-Poynter, Nicholas J.
Stevenson, Philip G.
Title Type 1 interferons and NK cells limit murine cytomegalovirus escape from the lymph node subcapsular sinus
Journal name PLoS Pathogens   Check publisher's open access policy
ISSN 1553-7374
Publication date 2016-12-07
Year available 2016
Sub-type Article (original research)
DOI 10.1371/journal.ppat.1006069
Open Access Status DOI
Volume 12
Issue 12
Start page e1006069
Total pages 22
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Subject 2405 Parasitology
2404 Microbiology
2403 Immunology
1312 Molecular Biology
1311 Genetics
2406 Virology
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.
Keyword Natural-Killer-Cells
Dendritic Cells
I Interferons
Activation Receptor
Viral Replication
Virus Infection
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 1060138
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Chemistry and Molecular Biosciences
Child Health Research Centre Publications
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