期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 208, 期 12, 页码 2357-2366出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20111171
关键词
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资金
- National Institutes of Health [AI081677, K23AI084855, UL1RR024143]
- Bill and Melinda Gates Foundation [38650]
- Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative of Bill and Melinda Gates Foundation [334]
- Genome Quebec
Adjuvants are critical for the success of vaccines. Agonists of microbial pattern recognition receptors (PRRs) are promising new adjuvant candidates. A mechanism through which adjuvants enhance immune responses is to stimulate innate immunity. We studied the innate immune response in humans to synthetic double-stranded RNA (polyinosinic: polycytidylic acid [poly IC] stabilized with poly-l-lysine [poly ICLC]), an agonist for toll-like receptor (TLR) 3, and the cytosolic RNA helicase MDA-5. Transcriptional analysis of blood samples from eight volunteers, after subcutaneous administration of poly ICLC, showed upregulation of genes involved in multiple innate immune pathways in all subjects, including interferon (IFN) and inflammasome signaling. Blocking type I IFN receptor ex vivo significantly dampened the response to poly IC. Comparative transcriptional analysis showed that several innate immune pathways were similarly induced in volunteers immunized with the highly efficacious yellow fever vaccine. Therefore, a chemically defined PRR agonist like poly ICLC can be a reliable and authentic microbial mimic for inducing innate immune responses in humans.
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