Measles virus-dendritic cell interaction via SLAM inhibits innate immunity: selective signaling through TLR4 but not other TLRs mediates suppression of IL-12 synthesis.
Two hallmarks of measles virus (MV) infection are the ability of the virus to cause immunosuppression and the resultant enhanced susceptibility of the infected host to microbial insults. We investigated the effect of MV infection on the ability of dendritic cells (DCs) to induce IL-12 via toll-like receptor (TLR) signaling. When infected with MV, transgenic mice which expressed human SLAM receptor on their DCs were defective in the selective synthesis of IL-12 in DCs in response to stimulation of TLR4 signaling, but not to engagements of TLR2, 3, 7 or 9. MV suppressed TLR4-mediated IL-12 induction in DCs even in the presence of co-stimulation with another ligand for TLR2, 3, 7, or 9. While MV V and C proteins were not responsible for IL-12 inhibition, interaction of MV hemagglutinin with human SLAM facilitated the suppression. These results suggest that MV, by altering DC function, renders them unresponsive to secondary pathogens via TLR4.
Hahm
Bumsuk
B
Viral-Immunobiology Laboratory, Departments of Molecular and Integrative Neurosciences and Infectology, IMM6, The Scripps Research Institute, La Jolla, CA 92037, USA. hahmb@scripps.edu <hahmb@scripps.edu>
Cho
Jae-Ho
JH
Oldstone
Michael B A
MB
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism; D015536:Down-Regulation; D006389:Hemagglutinins, Viral / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D018664:Interleukin-12 / Q000096:biosynthesis*; D008457:Measles / Q000276:immunology*; D008459:Measles virus / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D015398:Signal Transduction; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*
D015703:Antigens, CD; D006389:Hemagglutinins, Viral; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D018664:Interleukin-12