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Interleukin-32 isoforms: expression, interaction with interferon-regulated genes and clinical significance in chronically HIV-1-infected patients

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Abstract

Given the growing evidence for a role of interleukin-32 (IL-32) in the immune response to HIV-1 infection and its interplay with type I and III interferons (IFNs), we studied the gene expression of IL-32 isoforms (α and nonα) in untreated chronically HIV-1-infected patients and in gender- and age-matched healthy individuals. To further characterize both the anti-HIV properties of IL-32 and the cytokine’s relationship with host antiviral innate immune responses, we evaluated whether IL-32 can induce ex vivo the expression of antiviral IFN-induced genes (ISGs), namely myxovirus resistance A (MxA), and apolipoprotein B mRNA-editing enzyme catalytic (APOBEC)3G and APOBEC3F. We also investigated whether in vivo IL-32 (α and nonα) mRNA levels were correlated with those of MxA and APOBEC3G/3F. Results indicated that IL-32 (α and nonα) mRNA levels were significantly higher in HIV-1-infected patients than in healthy individuals. Furthermore, IL-32 (α and nonα) mRNA levels correlated negatively with HIV RNA levels, but not with the CD4+ T-cell count. Our ex vivo studies disclosed that ISGs mRNA levels were increased after IL-32γ treatment of peripheral blood mononuclear cells. Interestingly, significant positive correlations were found between transcript levels of both IL-32α and IL-32nonα and those of MxA and APOBEC3G/3F in untreated chronically HIV-1-infected patients. Overall, our results demonstrated that IL-32 isoforms are highly expressed during chronic HIV-1 infection and that IL-32 could have a central role in the antiviral immune response against HIV-1.

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Acknowledgments

This work was supported by a grant to Carolina Scagnolari from ISTITUTO PASTEUR, FONDAZIONE CENCI BOLOGNETTI (Finanziamento dei programmi di ricerca 2013–2015, Prot. 55/2013).

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Authors and Affiliations

  1. Pasteur Institute-Cenci Bolognetti Foundation, Department of Molecular Medicine, Laboratory of Virology, Sapienza University of Rome, Viale di Porta Tiburtina n 28, 00185, Rome, Italy

    Katia Monteleone, Pierluigi Di Maio, Giulia Cacciotti, Francesca Falasca, Maurizio Fraulo, Ombretta Turriziani & Carolina Scagnolari

  2. Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy

    Mario Falciano & Gabriella D’Ettorre

  3. Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy

    Ivano Mezzaroma

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  1. Katia Monteleone
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  2. Pierluigi Di Maio
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Correspondence to Carolina Scagnolari.

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Monteleone, K., Di Maio, P., Cacciotti, G. et al. Interleukin-32 isoforms: expression, interaction with interferon-regulated genes and clinical significance in chronically HIV-1-infected patients. Med Microbiol Immunol 203, 207–216 (2014). https://doi.org/10.1007/s00430-014-0329-2

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