期刊
CURRENT OPINION IN PHARMACOLOGY
卷 41, 期 -, 页码 128-136出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.coph.2018.05.012
关键词
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资金
- US National Institutes of Health (NIH) [AI095245, AI127658, AI080959]
- Searle Scholars Award
- Burroughs Wellcome Fund
- Crohn's and Colitis Foundation
- NIH [AI123284, AI073899, DK072201, DK111862]
Live attenuated vaccines elicit stronger protective immunity than dead vaccines. Distinct PAMPs designated as vita-PAMPs signify microbial viability to innate immune cells. Two vita-PAMPs have been characterized: cyclic-di-adenosine-monophosphate (c-di-AMP) and prokaryotic messenger RNA (mRNA). c-di-AMP produced by live Gram-positive bacteria elicits augmented production of STING-dependent type-I interferon, whereas prokaryotic mRNA from live bacteria is detected by TLR8 enabling discrimination of live from dead bacteria. Bacterial mRNA from live Gram-negative bacteria triggers a heightened type-I interferon and NLRP3 inflammasome response. By mobilizing unique viability associated innate responses, vita-PAMPs mobilize adaptive immunity that best elicits protection, including follicular T helper cell and antibody responses. Here, we review the molecular mechanisms that confer the unique adjuvanticity of vita-PAMPs and discuss their applications in vaccine design.
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