PMID- 29170665
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 8
DP  - 2017
TI  - Canonical Stimulation of the NLRP3 Inflammasome by Fungal Antigens Links Innate 
      and Adaptive B-Lymphocyte Responses by Modulating IL-1beta and IgM Production.
PG  - 1504
LID - 10.3389/fimmu.2017.01504 [doi]
LID - 1504
AB  - The NLRP3 inflammasome is activated in response to different bacterial, viral, 
      and fungal pathogens and serves as modulator of different pattern recognition 
      receptors signaling pathways. One of the main functions of NLRP3 is to 
      participate in IL-1beta maturation which is important in the host defense against 
      Pneumocystis and other fungal infections. However, dysregulation of NLRP3 and 
      IL-1beta secretion are also implicated in the pathophysiology of many 
      auto-inflammatory disorders. Often time's inflammatory flares are preceded by 
      infectious illnesses questioning the role of infection in autoimmune 
      exacerbations. However, we still do not fully understand the exact role that 
      infection or even colonization plays as a trigger of inflammation. Herein, we 
      investigated the role of NLRP3 in circulating B-lymphocytes following activation 
      with two major microbial antigens (beta-glucan and CpG). NLRP3 was determined 
      essential in two independent B-lymphocytes processes: pro-inflammatory cytokine 
      secretion and antibody regulation. Our results show that the beta-glucan fungal cell 
      wall carbohydrate stimulated B-lymphocytes to secrete IL-1beta in a process 
      partially mediated by Dectin-1 activation via SYK and the transcription factors 
      NF-kappaB and AP-1. This IL-1beta secretion was regulated by the NLRP3 inflammasome and 
      was dependent on potassium efflux and Caspase-1. Interestingly, B-lymphocytes 
      activated by unmethylated CpG motifs, found in bacterial and fungal DNA, failed 
      to induce IL-1beta. However, B-lymphocyte stimulation by CpG resulted in NLRP3 and 
      Caspase-1 activation and the production and secretion of IgM antibodies. 
      Furthermore, CpG-stimulated IgM secretion, unlike beta-glucan-mediated IL-1beta 
      production, was mediated by the mammalian target of rapamycin (mTOR). Inhibition 
      of NLRP3 and the mTOR pathway in CpG activated B-lymphocytes resulted in impaired 
      IgM secretion suggesting their participation in antibody regulation. In 
      conclusion, this study describes a differential response of NLRP3 to beta-glucan and 
      CpG antigens and identifies the NLRP3 inflammasome of human circulating 
      B-lymphocytes as a modulator of the innate and adaptive immune systems.
FAU - Ali, Mohamed F
AU  - Ali MF
AD  - The Thoracic Diseases Research Unit and the Division of Pulmonary and Critical 
      Care, Department of Medicine Mayo Clinic and Foundation, Rochester, MN, United 
      States.
FAU - Dasari, Harika
AU  - Dasari H
AD  - The Thoracic Diseases Research Unit and the Division of Pulmonary and Critical 
      Care, Department of Medicine Mayo Clinic and Foundation, Rochester, MN, United 
      States.
FAU - Van Keulen, Virginia P
AU  - Van Keulen VP
AD  - The Thoracic Diseases Research Unit and the Division of Pulmonary and Critical 
      Care, Department of Medicine Mayo Clinic and Foundation, Rochester, MN, United 
      States.
FAU - Carmona, Eva M
AU  - Carmona EM
AD  - The Thoracic Diseases Research Unit and the Division of Pulmonary and Critical 
      Care, Department of Medicine Mayo Clinic and Foundation, Rochester, MN, United 
      States.
LA  - eng
GR  - K08 HL112849/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20171109
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
PMC - PMC5684107
OTO - NOTNLM
OT  - B-lymphocytes
OT  - CpG
OT  - IL-1beta
OT  - IgM
OT  - NLRP3
OT  - fungi
OT  - inflammasome
OT  - beta-glucan
EDAT- 2017/11/25 06:00
MHDA- 2017/11/25 06:01
PMCR- 2017/01/01
CRDT- 2017/11/25 06:00
PHST- 2017/09/06 00:00 [received]
PHST- 2017/10/25 00:00 [accepted]
PHST- 2017/11/25 06:00 [entrez]
PHST- 2017/11/25 06:00 [pubmed]
PHST- 2017/11/25 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2017.01504 [doi]
PST - epublish
SO  - Front Immunol. 2017 Nov 9;8:1504. doi: 10.3389/fimmu.2017.01504. eCollection 
      2017.