Increased expression of IL-32 correlates with IFN-γ, Th1 and Tc1 in virologically suppressed HIV-1-infected patients. (August 2019)

• Record Type: Journal Article
• Authors: Santinelli, Letizia; Statzu, Maura; Pierangeli, Alessandra; Frasca, Federica; Bressan, Alessia; Pinacchio, Claudia; Nonne, Chiara; Turriziani, Ombretta; Antonelli, Guido; d'Ettorre, Gabriella; Scagnolari, Carolina
• Is Part Of: Cytokine. Volume 120(2019)
• Page Start: 273
• Page End: 281
• Publication Date: 2019-08
• Subjects: IL-32 -- HIV -- IFN gamma -- Gut -- T cell subtypes; IL-32 interleukin 32 -- IFN interferon -- PBMC peripheral blood mononuclear cells -- HAART highly active antiretroviral therapy -- LPL lamina propria lymphocytes -- EDTA ethylene-diamine-tetraacetic acid; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2019.01.012
• Languages: English
• ISSNs: 1043-4666

Abstract

Graphical abstract: Highlights: IL-32 levels in PBMCs remain elevated and fail to achieve normal expression in long-term treated HIV-1-infected patients. IL-32 mRNA expression levels increase with age in HIV-1-infected patients. IL-32 and IFN-γ establish an in vivo correlation in HIV-1-infected patients. IL-32 correlates negatively with gut-associated IFN-γ secreting T cell subpopulation frequencies in HIV-1-infected patients. Abstract: Following recent attention focused on IL-32 as an important component involved in the inflammatory cytokine network, we speculated that IL-32′s action on IFN-γ and IFN-γ secreting T cell subsets may help sustain the immune activation and dysregulation found in patients with HIV-1 achieving viral suppression. To explore this hypothesis, transcript levels of IL-32 and IFN-γ were evaluated in PBMC from 139 virologically suppressed HIV-1-infected patients and from 63 healthy individuals by Real Time RT-PCR assays. IL-32 and IFN-γ mRNA levels were also analyzed in CD4+ T cells, CD14+ monocytes and lamina propria lymphocytes (LPL) of the gut district in a subgroup of HIV-1-infected subjects. IFN-γ secreting CD4+ (Th1) and CD8+ (Tc1) T cell subset frequencies were evaluated in LPL by multiparametric flow cytometry. Gene expression results revealed that IL-32 and IFN-γ levels in PBMC from HIV-1-positive patients were significantly elevated compared to those from healthy donors, correlated with each other and increased with patient age. Both IL-32 and IFN-γ genes were also more strongly expressed in CD4+ T cells than in CD14+ monocytes. By contrast, IL-32 levels in LPL were comparable to those measured in PBMC, while IFN-γ levels were higher in PBMC than those in LPL. Negative correlations were found between IL-32 levels and the frequencies of Th1 and Tc1 subsets in gut mucosa. Collectively, our results provide the first evidence that IL-32 levels remain elevated in treated HIV-1-infected patients and correlate with IFN-γ, Th1 and Tc1 subsets.