Persistent virus infection inhibits type I interferon production by plasmacytoid dendritic cells to facilitate opportunistic infections.
Emerging studies indicate an association between virus-induced impairment in type I interferon (IFN-I) production and enhanced susceptibility to opportunistic infections, which represent a major health problem. Here, we provide in vivo evidence that lymphocytic choriomeningitis virus (LCMV) infection of its natural murine host dramatically diminishes the unique capacity of plasmacytoid dendritic cells (pDCs) to secrete high levels of systemic IFN-I. While both acute and persistent LCMV infections suppress pDC IFN-I response, only the persistent virus induces a long-lasting diversion of this innate immune pathway. The consequent reduction in IFN-I production serves to impair natural killer cell responses in LCMV-infected mice challenged subsequently with murine cytomegalovirus (MCMV) as an opportunistic pathogen. This innate defect also compromises the host's ability to counteract early MCMV spread. These findings provide a mechanistic explanation for the occurrence of opportunistic infections following viral insults and have important implications for treating such medical complications.
Department of Immunology and Microbial Sciences, Scripps Research Institute, La Jolla, CA 92037, USA. eizuniga@ucsd.edu
Elina I
EI
Zuniga
Li-Ying
LY
Liou
Lauren
L
Mack
Marilyn
M
Mendoza
Michael B A
MB
Oldstone
D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004198:Disease Susceptibility; D006566:Herpesviridae Infections / Q000276:immunology*; D007370:Interferon Type I / Q000096:biosynthesis* / Q000097:blood; D007694:Killer Cells, Natural / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000276:immunology*; D009894:Opportunistic Infections / Q000276:immunology*
D007370:Interferon Type I