PMID- 21602824
OWN - NLM
STAT- MEDLINE
DCOM- 20110726
LR  - 20231022
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 474
IP  - 7351
DP  - 2011 May 22
TI  - Detection of prokaryotic mRNA signifies microbial viability and promotes 
      immunity.
PG  - 385-9
LID - 10.1038/nature10072 [doi]
AB  - Live vaccines have long been known to trigger far more vigorous immune responses 
      than their killed counterparts. This has been attributed to the ability of live 
      microorganisms to replicate and express specialized virulence factors that 
      facilitate invasion and infection of their hosts. However, protective 
      immunization can often be achieved with a single injection of live, but not dead, 
      attenuated microorganisms stripped of their virulence factors. 
      Pathogen-associated molecular patterns (PAMPs), which are detected by the immune 
      system, are present in both live and killed vaccines, indicating that certain 
      poorly characterized aspects of live microorganisms, not incorporated in dead 
      vaccines, are particularly effective at inducing protective immunity. Here we 
      show that the mammalian innate immune system can directly sense microbial 
      viability through detection of a special class of viability-associated PAMPs 
      (vita-PAMPs). We identify prokaryotic messenger RNA as a vita-PAMP present only 
      in viable bacteria, the recognition of which elicits a unique innate response and 
      a robust adaptive antibody response. Notably, the innate response evoked by 
      viability and prokaryotic mRNA was thus far considered to be reserved for 
      pathogenic bacteria, but we show that even non-pathogenic bacteria in sterile 
      tissues can trigger similar responses, provided that they are alive. Thus, the 
      immune system actively gauges the infectious risk by searching PAMPs for 
      signatures of microbial life and thus infectivity. Detection of vita-PAMPs 
      triggers a state of alert not warranted for dead bacteria. Vaccine formulations 
      that incorporate vita-PAMPs could thus combine the superior protection of live 
      vaccines with the safety of dead vaccines.
FAU - Sander, Leif E
AU  - Sander LE
AD  - Immunology Institute, Department of Medicine, Mount Sinai School of Medicine, 
      1425 Madison Avenue, New York, New York 10029, USA.
FAU - Davis, Michael J
AU  - Davis MJ
FAU - Boekschoten, Mark V
AU  - Boekschoten MV
FAU - Amsen, Derk
AU  - Amsen D
FAU - Dascher, Christopher C
AU  - Dascher CC
FAU - Ryffel, Bernard
AU  - Ryffel B
FAU - Swanson, Joel A
AU  - Swanson JA
FAU - Muller, Michael
AU  - Muller M
FAU - Blander, J Magarian
AU  - Blander JM
LA  - eng
GR  - R01 AI064668/AI/NIAID NIH HHS/United States
GR  - T32 GM145304/GM/NIGMS NIH HHS/United States
GR  - R21 AI080959-01A1/AI/NIAID NIH HHS/United States
GR  - R01 AI095245/AI/NIAID NIH HHS/United States
GR  - AI080959A/AI/NIAID NIH HHS/United States
GR  - R21 AI080959/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110522
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Antibodies, Bacterial)
RN  - 0 (Bacterial Vaccines)
RN  - 0 (Carrier Proteins)
RN  - 0 (Inflammasomes)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, mouse)
RN  - 0 (RNA, Bacterial)
RN  - 0 (RNA, Messenger)
RN  - 0 (TICAM-1 protein, mouse)
RN  - 0 (Vaccines, Attenuated)
RN  - 0 (Vaccines, Inactivated)
RN  - 0 (Virulence Factors)
RN  - 77238-31-4 (Interferon-beta)
SB  - IM
EIN - Nature. 2011 Oct 6;478(7367):136
MH  - Adaptor Proteins, Vesicular Transport/deficiency/immunology
MH  - Animals
MH  - Antibodies, Bacterial/immunology
MH  - Bacteria/genetics/immunology/pathogenicity
MH  - Bacterial Vaccines/genetics/immunology
MH  - Carrier Proteins/metabolism
MH  - Cells, Cultured
MH  - Dendritic Cells/cytology/immunology/microbiology
MH  - Immunity, Innate/*immunology
MH  - Inflammasomes/immunology/metabolism
MH  - Interferon-beta/genetics/immunology
MH  - Macrophages/cytology/immunology/microbiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microbial Viability/*genetics/*immunology
MH  - NLR Family, Pyrin Domain-Containing 3 Protein
MH  - Phagocytosis
MH  - Phagosomes/immunology/microbiology
MH  - RNA, Bacterial/genetics/*immunology
MH  - RNA, Messenger/genetics/*immunology
MH  - Vaccines, Attenuated/genetics/immunology
MH  - Vaccines, Inactivated/immunology
MH  - Virulence Factors
PMC - PMC3289942
MID - NIHMS313007
EDAT- 2011/05/24 06:00
MHDA- 2011/07/27 06:00
PMCR- 2012/02/29
CRDT- 2011/05/24 06:00
PHST- 2010/04/30 00:00 [received]
PHST- 2011/03/24 00:00 [accepted]
PHST- 2011/05/24 06:00 [entrez]
PHST- 2011/05/24 06:00 [pubmed]
PHST- 2011/07/27 06:00 [medline]
PHST- 2012/02/29 00:00 [pmc-release]
AID - nature10072 [pii]
AID - 10.1038/nature10072 [doi]
PST - epublish
SO  - Nature. 2011 May 22;474(7351):385-9. doi: 10.1038/nature10072.