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Granulocytic MyeloidDerived Suppressor Cells Increased in Early Phases of Primary HIV Infection Depending on TRAIL Plasma Level

Tumino, Nicola PhD; Bilotta, Maria T. PhD; Pinnetti, Carmela MD; Ammassari, Adriana MD; Antinori, Andrea MD; Turchi, Federica MLT; Agrati, Chiara PhD; Casetti, Rita PhD; Bordoni, Veronica PhD; Cimini, Eleonora PhD; Abbate, Isabella PhD; Capobianchi, Maria R. PhD; Martini, Federico PhD; Sacchi, Alessandra PhD

JAIDS Journal of Acquired Immune Deficiency Syndromes: 15 April 2017 - Volume 74 - Issue 5 - p 575–582
doi: 10.1097/QAI.0000000000001283
Basic Science

Background: It has been demonstrated that myeloid-derived suppressor cells (MDSC) are expanded in HIV-1–infected individuals and correlated with disease progression. The phase of HIV infection during which MDSC expansion occurs, and the mechanisms that regulate this expansion remain to be established. In this study, we evaluated the frequency of MDSC in patients during primary HIV infection (PHI) and factors involved in MDSC control.

Methods: Patients with PHI and chronic HIV infection (CHI) were enrolled. PHI staging was performed according to Fiebig classification, and circulating MDSC frequency and function were evaluated by flow cytometry. Cytokine levels were evaluated by Luminex technology.

Results: We found that granulocytic MDSC (Gr-MDSC) frequency was higher in patients with PHI compared with healthy donors, but lower than that in patients with CHI. Interestingly, Gr-MDSC expansion was observed in the early phases of HIV infection (Fiebig II/III), but it was not associated with HIV viral load and CD4 T-cell count. Interestingly, in PHI, Gr-MDSC frequency was inversely correlated with plasmatic level of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), although a direct correlation was observed in CHI. Furthermore, lower level of Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) was observed in PHI compared with that in CHI. In vitro experiments demonstrated that, differently from CHI, recombinant TRAIL–induced apoptosis of Gr-MDSC from PHI, an effect that can be abrogated by GM-CSF.

Conclusion: We found that Gr-MDSC are expanded early during PHI and may be regulated by TRAIL and GM-CSF levels. These findings shed light on the fine mechanisms regulating the immune system during HIV infection and open new perspectives for immune-based strategies.

*Cellular Immunology Laboratory, “Lazzaro Spallanzani” National Institute for Infectious Diseases, IRCCS, Rome, Italy;

Clinical Division, “Lazzaro Spallanzani” National Institute for Infectious Diseases, IRCCS, Rome, Italy; and

Virology Laboratory, “Lazzaro Spallanzani” National Institute for Infectious Diseases, IRCCS, Rome, Italy.

Correspondence to: Alessandra Sacchi, PhD, National Institute for Infectious Diseases “Lazzaro Spallanzani”, IRCCS, Via Portuense 292, Rome 00149, Italy (e-mail: alessandra.sacchi@inmi.it).

Supported by grants from the Italian Ministry of Health (Ricerca Corrente) to INMI L. Spallanzani, IRCCS.

Part of the results were presented at the Italian Conference on AIDS and Retroviruses (ICAR); May 17–19, 2015; Riccione, Italy.

The authors have no conflicts of interest to disclose.

N.T., M.T.B., and F.M. contributed equally to this work.

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Received June 17, 2016

Accepted October 31, 2016

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