The anti-inflammatory IL-37/SIGIRR axis is functionally compromised in HIV infection.

AIDS 2019 09;33(11):1693-1703

Laboratory of Innate Immunity, CHU Ste-Justine Research Center/Department of Microbiology, Infectious Diseases & Immunology.

Background: IL-37 is a member of the IL-1 family with potent anti-inflammatory effects. Little is known about regulation of the cytokine and of its signaling co-receptor SIGIRR in HIV infection.

Objectives: Our main objective was to investigate how production of the cytokine and expression of SIGIRR on immune cells is regulated in HIV infection.

Methods: The study was conducted using biological samples from a cross section of HIV-infected individuals. Concentrations of IL-37, TNF-α and soluble form of SIGIRR in serum samples were determined by ELISA. The expression of SIGIRR on immune cells was determined by flow cytometry. IL-37 isoform-specific transcripts were determined in PBMC by RT-PCR using isoform-specific primers. The effects of exogenous IL-37 on HIV replication in human phytohaemagglutinin (PHA) blasts were determined in in-vitro assays.

Results: The cytokine concentrations tended to decrease in treatment-naive HIV-infected individuals. They were higher in treated HIV-infected individuals compared with those from treatment-naive ones. Higher concentrations of the cytokine were observed in sera from LTNP. The expression of SIGIRR on immune cells was decreased in HIV-infected individuals. On the other hand, its soluble form increased in the sera in these individuals. The trend was reversed in the patients undergoing antiretroviral treatment. Soluble SIGIRR attenuated anti-inflammatory effects of the cytokine. Serum IL-37 and soluble SIGIRR concentrations correlated with certain clinical parameters of the patients. Furthermore, recombinant human IL-37 inhibited HIV replication in human PHA blasts.

Conclusion: The IL-37/SIGIRR axis is functionally compromised in HIV-infected individuals. Targeting the axis may alleviate inflammation and decrease HIV replication in this viral infection.

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http://dx.doi.org/10.1097/QAD.0000000000002271DOI Listing
September 2019
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