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B7-H6-mediated downregulation of NKp30 in natural killer cells contributes to HIV-2 immune escape
- Source :
- AIDS, AIDS, Lippincott, Williams & Wilkins, 2019, 33 (1), pp.23-32. ⟨10.1097/QAD.0000000000002061⟩, AIDS. Official journal of the international AIDS Society, AIDS. Official journal of the international AIDS Society, 2019, 33 (1), pp.23-32. ⟨10.1097/QAD.0000000000002061⟩
- Publication Year :
- 2019
-
Abstract
- International audience; Objective: HIV-1 and HIV-2 differ notably in their epidemiology, with worldwide HIV-1 spread and HIV-2 mainly confined to West Africa. Natural killer (NK) cells are critical antiviral effectors of the immune system; however, limited information is available about these innate effector cells during HIV-2 infection.Method: In this study, 24 untreated HIV-2-infected patients were analyzed and compared with 21 long-term nonprogressor and 10 controller HIV-1 patients, and healthy donors. Extensive phenotype and functional NK-cell characteristics, as well as ligands of activating NK receptors involved in NK lysis were determined by flow cytometry.Results: We report in HIV-2 patients a very significant reduced expression of the activating NKp30 receptor (P < 0.0001) on NK cells, much higher than observed in HIV-1 patients. The impaired expression of NKp30 is correlated negatively with HLA-DR (r = -0.5970; P = 0.0002), and positively with both NKG2A (r = 0.5324; P < 0.0001) and Siglec-7 (r = 0.5621; P = 0.0004). HIV-2 patients with NKp30 NK cells displayed overproduction of IFN-γ (P < 0.0001) associated with impaired cytolytic function when tested against target cells expressing surface B7-H6. This cellular ligand of NKp30 is strongly detectable as a surface molecule on CD4 T cells infected by HIV-2.Conclusion: Altogether, our data suggested that the defective expression of NKp30 may be induced by the chronic engagement of this receptor by B7-H6 expressed on HIV-2-infected target cells. This represents a novel mechanism by which the chronic ligand exposure by the viral environment may subvert NK-cell-mediated function to establish persistent HIV-2 infection.
- Subjects :
- 0301 basic medicine
Adult
Male
B7 Antigens
[SDV]Life Sciences [q-bio]
Immunology
Down-Regulation
HIV Infections
[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity
Flow cytometry
03 medical and health sciences
Young Adult
0302 clinical medicine
Immune system
Downregulation and upregulation
Immunology and Allergy
Medicine
Humans
Interferon gamma
030212 general & internal medicine
Receptor
Immune Evasion
Natural Cytotoxicity Triggering Receptor 3
medicine.diagnostic_test
business.industry
Effector
Middle Aged
3. Good health
Killer Cells, Natural
[SDV] Life Sciences [q-bio]
Cytolysis
030104 developmental biology
Infectious Diseases
Cell culture
[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie
HIV-2
Female
[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
business
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 02699370 and 14735571
- Database :
- OpenAIRE
- Journal :
- AIDS, AIDS, Lippincott, Williams & Wilkins, 2019, 33 (1), pp.23-32. ⟨10.1097/QAD.0000000000002061⟩, AIDS. Official journal of the international AIDS Society, AIDS. Official journal of the international AIDS Society, 2019, 33 (1), pp.23-32. ⟨10.1097/QAD.0000000000002061⟩
- Accession number :
- edsair.doi.dedup.....3d76e35cea8a2772c22e6acf5823ca9a