Type 1 Interferons and NK Cells Limit Murine Cytomegalovirus Escape from the Lymph Node Subcapsular Sinus

PLoS Pathogens

Nicholas J. Davis-Poynter¹  Rhonda D. Cardin²  Helen E. Farrell³  Kimberley Bruce³  Philip G. Stevenson³  Clara Lawler³ 

[1] Child Health Research Centre, University of Queensland, Brisbane, Australia;Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, United States of America;School of Chemistry and Molecular Biosciences and Child Health Research Centre, University of Queensland, Brisbane, Australia

关键词: NK cells;    Antibodies;    DAPI staining;    Spleen;    Cytomegalovirus infection;    Virions;    Vesicular stomatitis virus;    Cell staining;   

DOI  :  10.1371/journal.ppat.1006069

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY