Cutting edge: cooperation of IPS-1- and TRIF-dependent pathways in poly IC-enhanced antibody production and cytotoxic T cell responses.
Double-stranded RNA, polyriboinosinic-polyribocytidylic acid (poly IC), acts as an adjuvant that enhances adaptive immune responses. The recognition of poly IC is mediated by endosomal TLR3 and cytoplasmic RNA helicase melanoma differentiation-associated gene 5 (Mda5), which signal through the adaptors Toll/IL-1R domain-containing adaptor inducing IFN-beta (TRIF) and IFN-beta promoter stimulator-1 (IPS-1), respectively. However, the contribution of these pathways to the adjuvant effects of poly IC remains unclear. In this study, we found that poly IC-enhanced, Ag-specific Ab production was severely decreased in IPS-1-deficient mice but not in TRIF-deficient mice. However, the double deficiency resulted in a complete loss of Ab production. Furthermore, Ag-specific CD8+ T cell expansion was reduced in both IPS-1-deficient and TRIF-deficient mice and entirely abrogated in the doubly deficient mice. Taken together, these results demonstrate that the adjuvant effects of poly IC require a cooperative activation of TLR and cytoplasmic RNA helicase pathways.
Kumar
Himanshu
H
Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
Koyama
Shohei
S
Ishii
Ken J
KJ
Kawai
Taro
T
Akira
Shizuo
S
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D011070:Poly I-C / Q000276:immunology / Q000494:pharmacology*; D020365:RNA Helicases / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000819:agonists
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000276:Adjuvants, Immunologic; D011070:Poly I-C; D020365:RNA Helicases; D051196:Toll-Like Receptor 3; C512612:MAVS protein, mouse; C476286:Ticam1 protein, mouse; C519703:TLR3 protein, mouse