Abstract
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 immunebased strategies.
| Original language | English |
|---|---|
| Pages (from-to) | 575-582 |
| Number of pages | 8 |
| Journal | Journal of Acquired Immune Deficiency Syndromes |
| Volume | 74 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Apr 15 2017 |
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Keywords
- Fiebig classification
- HIV
- Immune suppression
- MDSC
- Primary infection
- TRAIL
ASJC Scopus subject areas
- Infectious Diseases
- Pharmacology (medical)
Cite this
Granulocytic myeloid-derived suppressor cells increased in early phases of primary HIV infection depending on TRAIL plasma level. / Tumino, Nicola; Bilotta, Maria T.; Pinnetti, Carmela; Ammassari, Adriana; Antinori, Andrea; Turchi, Federica; Agrati, Chiara; Casetti, Rita; Bordoni, Veronica; Cimini, Eleonora; Abbate, Isabella; Capobianchi, Maria R.; Martini, Federico; Sacchi, Alessandra.
In: Journal of Acquired Immune Deficiency Syndromes, Vol. 74, No. 5, 15.04.2017, p. 575-582.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Granulocytic myeloid-derived suppressor cells increased in early phases of primary HIV infection depending on TRAIL plasma level
AU - Tumino, Nicola
AU - Bilotta, Maria T.
AU - Pinnetti, Carmela
AU - Ammassari, Adriana
AU - Antinori, Andrea
AU - Turchi, Federica
AU - Agrati, Chiara
AU - Casetti, Rita
AU - Bordoni, Veronica
AU - Cimini, Eleonora
AU - Abbate, Isabella
AU - Capobianchi, Maria R.
AU - Martini, Federico
AU - Sacchi, Alessandra
PY - 2017/4/15
Y1 - 2017/4/15
N2 - 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 immunebased strategies.
AB - 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 immunebased strategies.
KW - Fiebig classification
KW - HIV
KW - Immune suppression
KW - MDSC
KW - Primary infection
KW - TRAIL
UR - http://www.scopus.com/inward/record.url?scp=85008312153&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85008312153&partnerID=8YFLogxK
U2 - 10.1097/QAI.0000000000001283
DO - 10.1097/QAI.0000000000001283
M3 - Article
AN - SCOPUS:85008312153
VL - 74
SP - 575
EP - 582
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
SN - 1525-4135
IS - 5
ER -