The NLRP3 Inflammasome Is Upregulated in HIV-Infected Antiretroviral Therapy-Treated Individuals with Defective Immune Recovery

Inflammasome-mediated activation of caspase-1 regulates inflammatory responses and pyroptosis. We analyzed possible associations between inflammasome-related genes and immune reconstitution in HIV-infected antiretroviral therapy (ART)-treated patients. Cross-sectional, case-control study. HIV-infect...

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Vydáno v:Frontiers in immunology Ročník 9; s. 214
Hlavní autoři: Bandera, Alessandra, Masetti, Michela, Fabbiani, Massimiliano, Biasin, Mara, Muscatello, Antonio, Squillace, Nicola, Clerici, Mario, Gori, Andrea, Trabattoni, Daria
Médium: Journal Article
Jazyk:angličtina
Vydáno: Switzerland Frontiers Media S.A 12.02.2018
Témata:
Adult
Aged
Animals
Anti-HIV Agents - therapeutic use
Case-Control Studies
caspase
Caspase 1 - immunology
Caspase 1 - metabolism
Cross-Sectional Studies
Female
HIV
HIV Infections - drug therapy
HIV Infections - immunology
HIV Infections - virology
HIV-1 - genetics
HIV-1 - immunology
HIV-1 - isolation & purification
Humans
immune reconstitution
Immune Reconstitution - immunology
Immunology
inflammasome
Inflammasomes - immunology
Inflammasomes - metabolism
Leukocytes, Mononuclear
Male
Mice
Middle Aged
NLR Family, Pyrin Domain-Containing 3 Protein - immunology
NLR Family, Pyrin Domain-Containing 3 Protein - metabolism
pyroptosis
RNA, Viral - isolation & purification
Treatment Outcome
Up-Regulation
pyroptosis
immune reconstitution
HIV
inflammasome
caspase
ISSN:1664-3224, 1664-3224
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Shrnutí:Inflammasome-mediated activation of caspase-1 regulates inflammatory responses and pyroptosis. We analyzed possible associations between inflammasome-related genes and immune reconstitution in HIV-infected antiretroviral therapy (ART)-treated patients. Cross-sectional, case-control study. HIV-infected patients on ART for ≥24 months with HIV-RNA<50 cp/mL for ≥12 months were enrolled and defined as immunological responders (IR) or non-responders (INR) if CD4 count was ≥500 or ≤350 cells/μL, respectively. Expression of inflammasome genes, caspases 1, 3, 4, 5 and γ-interferon-inducible protein 16 (IFI16) was measured in unstimulated and LPS- or aldrithiol-2-treated HIV-1 virions-stimulated peripheral blood mononuclear cells. Microbial translocation markers were evaluated. Thirty-nine patients (22 IRs; 17 INRs) were enrolled. LPS-stimulated inflammasome genes were significantly upregulated in INRs. Whereas HIV-1 stimulation induced (NOD)-like receptor (NLR) family pyrin domain containing 3 (NLRP3) expression in both IRs and INRs, NLRP3 and IL-18 expression was significantly increased in INRs compared to IRs. Significant higher caspase-1 expression was seen as well, whereas caspase 3, 4, and 5 expression was similar in both groups. No differences in microbial translocation markers (LPS and soluble CD14) were detected in the two groups. Upregulation of NLRP3 and caspase-1 is observed in INR patients. This could play a role in persistent immune activation that characterize INRs. Caspase-1 upregulation could induce CD4 T-cell loss pyroptosis, contributing to unsatisfactory CD4 T-cells recovery.
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content type line 23
Edited by: Francesca Chiodi, Karolinska Institute (KI), Sweden
Reviewed by: Vicente Estrada, Hospital Clínico San Carlos, Spain; Kehmia Titanji, Emory University School of Medicine, United States
Specialty section: This article was submitted to HIV and AIDS, a section of the journal Frontiers in Immunology
These authors have contributed equally to the work.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2018.00214