Cutting edge: Overlapping functions of TLR7 and TLR9 for innate defense against a herpesvirus infection.
As initially demonstrated with murine cytomegalovirus (MCMV), plasmacytoid dendritic cells (pDCs) are the major source of IFN-alpha/beta in response to a variety of viruses in vivo. However, contradictory results have been obtained pertaining to the mechanisms promoting IFN-alpha/beta production by pDCs in response to MCMV. In this study we show that TLR7 and TLR9 exert redundant functions for IFN-alpha/beta, IL-12p40, and TNF-alpha production by pDCs in vivo during MCMV infection. In contrast, we confirm that systemic production of IL-12p70 strictly depends on TLR9. The combined loss of TLR7 and TLR9 recapitulates critical features of the phenotype of MyD88-deficient mice, including a dramatic decrease in systemic IFN-alpha/beta levels, an increase in viral load, and increased susceptibility to MCMV-induced mortality. This is the first demonstration of the implication of TLR7 in the recognition of a DNA virus.
Zucchini
Nicolas
N
Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Parc Scientifique de Luminy, Marseille Cedex 09, France.
Bessou
Gilles
G
Traub
Stephanie
S
Robbins
Scott H
SH
Uematsu
Satoshi
S
Akira
Shizuo
S
Alexopoulou
Lena
L
Dalod
Marc
M
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate / Q000235:genetics; D016898:Interferon-alpha / Q000235:genetics / Q000276:immunology; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000235:genetics / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D019562:Viral Load
D016898:Interferon-alpha; D053762:Interleukin-12 Subunit p40; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C477038:Tlr7 protein, mouse; C495370:Tlr9 protein, mouse; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta