Background: 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. Methods: 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-1BaL virions-stimulated peripheral blood mononuclear cells. Microbial translocation markers were evaluated. Results: Thirty-nine patients (22 IRs; 17 INRs) were enrolled. LPS-stimulated inflammasome genes were significantly upregulated in INRs. Whereas HIV-1BaL 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. Conclusion: 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 via pyroptosis, contributing to unsatisfactory CD4 T-cells recovery.
The NLRP3 Inflammasome Is Upregulated in HIV-Infected Antiretroviral Therapy-Treated Individuals with Defective Immune Recovery / A. Bandera, M. Masetti, M. Fabbiani, M. Biasin, A. Muscatello, N. Squillace, M.S. Clerici, A. Gori, D.L. Trabattoni. - In: FRONTIERS IN IMMUNOLOGY. - ISSN 1664-3224. - 9(2018 Feb 12), pp. 214.1-214.8.
|Titolo:||The NLRP3 Inflammasome Is Upregulated in HIV-Infected Antiretroviral Therapy-Treated Individuals with Defective Immune Recovery|
|Parole Chiave:||HIV; caspase; immune reconstitution; inflammasome; pyroptosis|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
Settore BIO/13 - Biologia Applicata
Settore MED/17 - Malattie Infettive
|Data di pubblicazione:||12-feb-2018|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3389/fimmu.2018.00214|
|Appare nelle tipologie:||01 - Articolo su periodico|