PMID- 29135573
OWN - NLM
STAT- In-Data-Review
LR  - 20180111
IS  - 1473-5571 (Electronic)
IS  - 0269-9370 (Linking)
VI  - 32
IP  - 3
DP  - 2018 Jan 28
TI  - Evidence of inflammasome activation and formation of monocyte-derived ASC specks 
      in HIV-1 positive patients.
PG  - 299-307
LID - 10.1097/QAD.0000000000001693 [doi]
AB  - OBJECTIVE: The formation of large intracellular protein aggregates of the
      inflammasome adaptor protein ASC (apoptosis-associated speck-like protein
      containing a caspase-recruitment domain; also know as PYCARD) is a hallmark of
      inflammasome activation. ASC speck-forming cells release the highly
      proinflammatory cytokine IL-1beta in addition to ASC specks into the
      extracellular space during pyroptotic cell death. There ASC specks can propagate 
      inflammation to other nonactivated cells or tissues. HIV-1 retroviral infection
      triggers inflammasome activation of abortively infected CD4(+) T cells in
      secondary lymphatic tissues. However, if pyroptosis occurs in other peripheral
      blood mononuclear cells (PBMCs) of HIV-1-infected patients is currently unknown. 
      We investigated if ASC speck positive cells are present in the circulation of
      HIV-1-infected patients. DESIGN AND METHODS: PBMCs or plasma of HIV-1 infected,
      antiretroviral therapy-naive patients were analyzed for the presence of ASC
      speck(+) cells or extracellular ASC and compared with healthy controls.
      Intracellular staining for ASC was employed to detect ASC speck(+) cells within
      PBMCs by flow cytometry, and ELISA to detect free ASC in the plasma. ASC
      multimerization was confirmed by immunoblot. RESULTS: Peripheral blood
      CD14(+)(+)CD16(-) monocytes were ASC speck(+) in HIV patients, but not in healthy
      controls. In the subgroup analysis, HIV patients with lower CD4(+) T-cell counts 
      and higher viral load had significantly more ASC speck(+) monocytes. ASC speck
      formation did not correlate with Gag expression, coinfection, lactate
      dehydrogenase or C-reactive protein. CONCLUSION: Our findings suggest that
      pyroptotic CD14(+)(+)CD16(-) classical monocytes of HIV-1-infected patients
      release ASC specks into the blood stream, a phenomenon that may contribute to
      HIV-1 induced inflammation and immune activation.
FAU - Ahmad, Fareed
AU  - Ahmad F
AD  - Department of Clinical Immunology and Rheumatology, Hannover Medical School,
      Hannover.
AD  - Department of Dermatology, University of Heidelberg, Heidelberg.
FAU - Mishra, Neha
AU  - Mishra N
AD  - Department of Medicine A, Section of Rheumatology, University Medicine
      Greifswald, Greifswald.
FAU - Ahrenstorf, Gerrit
AU  - Ahrenstorf G
AD  - Department of Clinical Immunology and Rheumatology, Hannover Medical School,
      Hannover.
FAU - Franklin, Bernardo S
AU  - Franklin BS
AD  - Institute of Innate Immunity, University Hospitals Bonn, University of Bonn,
      Bonn, Germany.
FAU - Latz, Eicke
AU  - Latz E
AD  - Institute of Innate Immunity, University Hospitals Bonn, University of Bonn,
      Bonn, Germany.
AD  - Department of Infectious Diseases and Immunology, University of Massachusetts
      Medical School, Worcester, Massachusetts, USA.
FAU - Schmidt, Reinhold E
AU  - Schmidt RE
AD  - Department of Clinical Immunology and Rheumatology, Hannover Medical School,
      Hannover.
FAU - Bossaller, Lukas
AU  - Bossaller L
AD  - Department of Medicine A, Section of Rheumatology, University Medicine
      Greifswald, Greifswald.
LA  - eng
PT  - Journal Article
PL  - England
TA  - AIDS
JT  - AIDS (London, England)
JID - 8710219
EDAT- 2017/11/15 06:00
MHDA- 2017/11/15 06:00
CRDT- 2017/11/15 06:00
PHST- 2017/11/15 06:00 [pubmed]
PHST- 2017/11/15 06:00 [medline]
PHST- 2017/11/15 06:00 [entrez]
AID - 10.1097/QAD.0000000000001693 [doi]
PST - ppublish
SO  - AIDS. 2018 Jan 28;32(3):299-307. doi: 10.1097/QAD.0000000000001693.