Cutting edge: cooperation of IPS-1- and TRIF-dependent pathways in poly IC-enhanced antibody production and cytotoxic T cell responses.

Abstract

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.

• Authors: Himanshu Kumar, Shohei Koyama, Ken J Ishii, Taro Kawai, Shizuo Akira
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 180 Issue 2 Pg. 683-7 (Jan 15 2008) ISSN: 0022-1767 [Print] United States
• PMID: 18178804 (Publication Type: Journal Article)

Chemical References

• Adaptor Proteins, Signal Transducing
• Adaptor Proteins, Vesicular Transport
• Adjuvants, Immunologic
• IPS-1 protein, mouse
• TICAM-1 protein, mouse
• TLR3 protein, mouse
• Toll-Like Receptor 3
• RNA Helicases
• Poly I-C

Topics

• Adaptor Proteins, Signal Transducing (genetics, metabolism)
• Adaptor Proteins, Vesicular Transport (genetics, metabolism)
• Adjuvants, Immunologic (pharmacology)
• Animals
• Antibody Formation (drug effects, genetics)
• Mice
• Mice, Knockout
• Poly I-C (immunology, pharmacology)
• RNA Helicases (metabolism)
• T-Lymphocytes, Cytotoxic (drug effects, immunology)
• Toll-Like Receptor 3 (agonists)