PMID- 21876553
OWN - NLM
STAT- MEDLINE
DCOM- 20130115
LR  - 20221207
IS  - 1440-1711 (Electronic)
IS  - 0818-9641 (Print)
IS  - 0818-9641 (Linking)
VI  - 90
IP  - 6
DP  - 2012 Jul
TI  - Mycobacterium abscessus activates the NLRP3 inflammasome via Dectin-1-Syk and 
      p62/SQSTM1.
PG  - 601-10
LID - 10.1038/icb.2011.72 [doi]
AB  - Numerous atypical mycobacteria, including Mycobacterium abscessus (Mabc), cause 
      nontuberculous mycobacterial infections, which present a serious public health 
      threat. Inflammasome activation is involved in host defense and the pathogenesis 
      of autoimmune diseases. However, inflammasome activation has not been widely 
      characterized in human macrophages infected with atypical mycobacteria. Here, we 
      demonstrate that Mabc robustly activates the nucleotide binding and 
      oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) 
      inflammasome via dectin-1/Syk-dependent signaling and the cytoplasmic scaffold 
      protein p62/SQSTM1 (p62) in human macrophages. Both dectin-1 and Toll-like 
      receptor 2 (TLR2) were required for Mabc-induced mRNA expression of 
      pro-interleukin (IL)-1beta, cathelicidin human cationic antimicrobial 
      protein-18/LL-37 and beta-defensin 4 (DEFB4). Dectin-1-dependent Syk signaling, but 
      not that of MyD88, led to the activation of caspase-1 and secretion of IL-1beta 
      through the activation of an NLRP3/apoptosis-associated speck-like protein 
      containing a caspase recruitment domain (ASC) inflammasome. Additionally, 
      potassium efflux was required for Mabc-induced NLRP3/ASC inflammasome activation. 
      Furthermore, Mabc-induced p62 expression was critically involved in NLRP3 
      inflammasome activation in human macrophages. Finally, NLRP3/ASC was critical for 
      the inflammasome in antimicrobial responses to Mabc infection. Taken together, 
      these data demonstrate the induction mechanism of the NLRP3/ASC inflammasome and 
      its role in innate immunity to Mabc infection.
FAU - Lee, Hye-Mi
AU  - Lee HM
AD  - Department of Microbiology, Chungnam National University School of Medicine, 
      Daejeon, Korea.
FAU - Yuk, Jae-Min
AU  - Yuk JM
FAU - Kim, Ki-Hye
AU  - Kim KH
FAU - Jang, Jichan
AU  - Jang J
FAU - Kang, Gun
AU  - Kang G
FAU - Park, Jin Bong
AU  - Park JB
FAU - Son, Ji-Woong
AU  - Son JW
FAU - Jo, Eun-Kyeong
AU  - Jo EK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110830
PL  - United States
TA  - Immunol Cell Biol
JT  - Immunology and cell biology
JID - 8706300
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antimicrobial Cationic Peptides)
RN  - 0 (CLEC7A protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cathelicidins)
RN  - 0 (DEFB4A protein, human)
RN  - 0 (Inflammasomes)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Lectins, C-Type)
RN  - 0 (MYD88 protein, human)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (NLRP3 protein, human)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (SQSTM1 protein, human)
RN  - 0 (Sequestosome-1 Protein)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (beta-Defensins)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (SYK protein, human)
RN  - EC 2.7.10.2 (Syk Kinase)
RN  - EC 3.4.22.36 (Caspase 1)
RN  - RWP5GA015D (Potassium)
SB  - IM
CIN - Immunol Cell Biol. 2012 Jul;90(6):568-70. PMID: 21989418
MH  - Adaptor Proteins, Signal Transducing/*metabolism
MH  - Antimicrobial Cationic Peptides
MH  - Carrier Proteins/*metabolism
MH  - Caspase 1/genetics/metabolism
MH  - Cathelicidins/biosynthesis
MH  - Cell Line
MH  - Humans
MH  - Inflammasomes/*immunology/metabolism
MH  - Interleukin-1beta/biosynthesis/genetics
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Lectins, C-Type/*metabolism
MH  - Macrophages/*immunology/*microbiology
MH  - Mycobacterium Infections, Nontuberculous/immunology
MH  - Myeloid Differentiation Factor 88
MH  - NLR Family, Pyrin Domain-Containing 3 Protein
MH  - Nontuberculous Mycobacteria/*immunology
MH  - Potassium/metabolism
MH  - Protein-Tyrosine Kinases/*metabolism
MH  - RNA Interference
MH  - RNA, Small Interfering
MH  - Sequestosome-1 Protein
MH  - Signal Transduction
MH  - Syk Kinase
MH  - Toll-Like Receptor 2/genetics/metabolism
MH  - beta-Defensins/biosynthesis
PMC - PMC3389799
EDAT- 2011/08/31 06:00
MHDA- 2013/01/16 06:00
CRDT- 2011/08/31 06:00
PHST- 2011/08/31 06:00 [entrez]
PHST- 2011/08/31 06:00 [pubmed]
PHST- 2013/01/16 06:00 [medline]
AID - icb201172 [pii]
AID - 10.1038/icb.2011.72 [doi]
PST - ppublish
SO  - Immunol Cell Biol. 2012 Jul;90(6):601-10. doi: 10.1038/icb.2011.72. Epub 2011 Aug 
      30.