Lars Jørgen Østergaard

Innate DNA sensing is impaired in HIV patients and IFI16 expression correlates to chronic immune activation

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The innate immune system has been recognized to play a role in the pathogenesis of HIV infection, both by stimulating protective activities, and through contribution to chronic immune activation, the development of immunodeficiency, and progression to AIDS. A role for DNA sensors in HIV recognition has recently been suggested, and the aim of the present study was to describe the influence of HIV infection on expression and function of intracellular DNA sensing. Here we demonstrate impaired expression of interferon-stimulated genes in responses to DNA in PBMCs from HIV positive individuals, irrespective of whether patients receive antiretroviral treatment. Furthermore, we show that expression levels of the DNA sensors IFI16 and cGAS were increased in treatment-naïve patients, and for IFI16 expression was correlated with high viral load and low CD4 cell count. Finally, our data demonstrate a correlation between IFI16 and CD38 expression, a marker of immune activation, in CD4+ central and effector memory T cells, which may indicate that IFI16-mediated DNA sensing and signaling contributes to chronic immune activation. Altogether, the present study demonstrates abnormal expression and function of cytosolic DNA sensors in HIV patients, which may have implications for control of opportunistic infections, chronic immune activation, and T cell death.
Original languageEnglish
JournalClinical and Experimental Immunology
Pages (from-to)295-309
Number of pages15
Publication statusPublished - 5 Mar 2014

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