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Cytokine. 2018 Aug 20;111:97-105. doi: 10.1016/j.cyto.2018.08.018. [Epub ahead of print]

A high-resolution mass cytometry analysis reveals a delay of cytokines production after TLR4 or TLR7/8 engagements in HIV-1 infected humans.

Author information

1
CEA - Université Paris Sud 11 - Inserm U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, 92265 Fontenay-aux-Roses, France. Electronic address: adrien.leite-pereira@cea.fr.
2
CEA - Université Paris Sud 11 - Inserm U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, 92265 Fontenay-aux-Roses, France.
3
CEA - Université Paris Sud 11 - Inserm U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, 92265 Fontenay-aux-Roses, France; APHP, Hôpitaux Universitaires Paris Sud, Service de Médecine Interne-Immunologie Clinique, 94276 Le Kremin-Bicêtre, France.
4
CEA - Université Paris Sud 11 - Inserm U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, 92265 Fontenay-aux-Roses, France. Electronic address: antonio.cosma@cea.fr.

Abstract

HIV infection is associated with chronic inflammation in both non-treated and treated patients. TLR-dependent mechanisms are strongly involved in the maintenance of this inflammation. Indeed, the residual replication of HIV, the potential viral co-infections, or the products issued from microbial translocation provide TLR ligands, which contribute to trigger innate immune responses. Maintaining this chronic inflammation leads to an exhaustion of the immune system. Therefore, the TLR-dependent responses could be altered in HIV-infected patients. To investigate this hypothesis, we performed high-resolution phenotyping using a mass cytometry panel of 34 cell markers. Whole blood cells from healthy, non-treated HIV-infected and ART-treated HIV-infected subjects were stimulated with LPS, R848 or Poly(I:C). We observed the immune responses induced in T-cells, B-cells, polymorphonuclear cells, NK cells, basophils, monocytes and dendritic cells. We observed that, for either LPS or R848 stimulations, the production of cytokines in monocytes and conventional dendritic cells was delayed in treated or non-treated HIV-infected patients, compared to healthy individuals. These results suggest that leukocytes from chronic HIV-infected patients are slower to respond following the sensing of pathogens and danger signals, which may be an important feature of HIV infection.

KEYWORDS:

Cytokines; HIV infection; Mass cytometry; TLR stimulations

PMID:
30138900
DOI:
10.1016/j.cyto.2018.08.018
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