Toll-like receptor 7 is required for effective adaptive immune responses that prevent persistent virus infection.
TLR7 is an innate signaling receptor that recognizes single-stranded viral RNA and is activated by viruses that cause persistent infections. We show that TLR7 signaling dictates either clearance or establishment of life-long chronic infection by lymphocytic choriomeningitis virus (LCMV) Cl 13 but does not affect clearance of the acute LCMV Armstrong 53b strain. TLR7(-/-) mice infected with LCMV Cl 13 remained viremic throughout life from defects in the adaptive antiviral immune response-notably, diminished T cell function, exacerbated T cell exhaustion, decreased plasma cell maturation, and negligible antiviral antibody production. Adoptive transfer of TLR7(+/+) LCMV immune memory cells that enhanced clearance of persistent LCMV Cl 13 infection in TLR7(+/+) mice failed to purge LCMV Cl 13 infection in TLR7(-/-) mice, demonstrating that a TLR7-deficient environment renders antiviral responses ineffective. Therefore, methods that promote TLR7 signaling are promising treatment strategies for chronic viral infections.
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Kevin B
KB
Walsh
John R
JR
Teijaro
Elina I
EI
Zuniga
Megan J
MJ
Welch
Daniel M
DM
Fremgen
Shawn D
SD
Blackburn
Karl F
KF
von Tiehl
E John
EJ
Wherry
Richard A
RA
Flavell
Michael B A
MB
Oldstone
D019264:Adoptive Transfer; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010950:Plasma Cells / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000276:immunology*
D000914:Antibodies, Viral; D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7