title: Analysis of inflammasomes and antiviral sensing components reveals decreased expression of NLRX1 in HIV-positive patients assuming efficient antiretroviral therapy.
abstract: OBJECTIVE
  Few studies have investigated the importance of different components of the inflammasome system and of innate mitochondrial sensing (IMS) pathways in HIV infection and its treatment. We analysed the expression of several components of the inflammasome and of the IMS in HIV-positive patients taking successful combination antiretroviral therapy (cART).
  
  
  METHODS
  We enrolled 20 HIV-positive patients under cART, who achieved viral suppression since at least 10 months and 20 age and sex-matched healthy donors. By RT-PCR, using peripheral blood mononuclear cells (PBMCs), we quantified the mRNA expression of 16 genes involved in inflammasome activation and regulation (AIM2, NAIP, PYCARD, CASP1, CASP5, NLRP6, NLRP1, NLRP3, TXNIP, BCL2, NLRC4, PANX1, P2RX7, IL-18, IL-1β, SUGT1) and eight genes involved in IMS (MFN2, MFN1, cGAS, RIG-I, MAVS, NLRX1, RAB32, STING).
  
  
  RESULTS
  Compared with controls, HIV-positive patients showed significantly lower mRNA levels of the mitochondrial protein NLRX1, which plays a key role in regulating apoptotic cell death; main PBMC subpopulations behave in a similar manner. No differences were observed in the expression of inflammasome components, which however showed complex correlations.
  
  
  CONCLUSIONS
  The decreased level of NLRX1 in HIV infection could suggest that the virus is able to downregulate mechanisms linked to triggering of cell death in several immune cell types. The fact that HIV-positive patients did not show altered expression of inflammasome components, nor of most genes involved in IMS, suggests that the infection and/or the chronic immune activation does not influence the transcriptional machinery of innate mechanisms able to trigger inflammation at different levels.
authors.affiliation: aDepartment of Surgery, Medicine, Dentistry and Morphological Sciences bDepartment of Life Sciences cDepartment of Medical and Surgical Sciences of Mother, Child and Adult, University of Modena and Reggio Emilia dInfectious Diseases Clinics, Azienda Ospedaliero-Universitaria Policlinico di Modena eDipartimento Sperimentale Interaziendale, Campus San Lazzaro, Reggio Emilia, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Nasi
authors.forename: Sara
authors.initials: S
authors.lastname: De Biasi
authors.forename: Elena
authors.initials: E
authors.lastname: Bianchini
authors.forename: Margherita
authors.initials: M
authors.lastname: Digaetano
authors.forename: Marcello
authors.initials: M
authors.lastname: Pinti
authors.forename: Lara
authors.initials: L
authors.lastname: Gibellini
authors.forename: Simone
authors.initials: S
authors.lastname: Pecorini
authors.forename: Gianluca
authors.initials: G
authors.lastname: Carnevale
authors.forename: Giovanni
authors.initials: G
authors.lastname: Guaraldi
authors.forename: Vanni
authors.initials: V
authors.lastname: Borghi
authors.forename: Cristina
authors.initials: C
authors.lastname: Mussini
authors.forename: Andrea
authors.initials: A
authors.lastname: Cossarizza
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D005260:Female; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000032:analysis*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000032:analysis*; D060888:Real-Time Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000032:analysis*
chemical_list: D044966:Anti-Retroviral Agents; D058847:Inflammasomes; D024101:Mitochondrial Proteins; C527006:NLRX1 protein, human; D011971:Receptors, Immunologic