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Sci Rep. 2018 Nov 21;8(1):17215. doi: 10.1038/s41598-018-35478-1.

HIV-1 Envelope Glycoproteins Induce the Production of TNF-α and IL-10 in Human Monocytes by Activating Calcium Pathway.

Author information

1
INSERM, U1043, Toulouse, France.
2
CNRS, U5282, Toulouse, France.
3
University Paul-Sabatier, Toulouse, France.
4
Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA, 92697, United States of America.
5
INSERM, U1043, Toulouse, France. elmostafa.bahraoui@univ-tlse3.fr.
6
CNRS, U5282, Toulouse, France. elmostafa.bahraoui@univ-tlse3.fr.
7
University Paul-Sabatier, Toulouse, France. elmostafa.bahraoui@univ-tlse3.fr.

Abstract

Human HIV-1 infection leads inevitably to a chronic hyper-immune-activation. However, the nature of the targeted receptors and the pathways involved remain to be fully elucidated. We demonstrate that X4-tropic gp120 induced the production of TNF-α and IL-10 by monocytes through activation of a cell membrane receptor, distinct from the CD4, CXCR4, and MR receptors. Gp120 failed to stimulate IL-10 and TNF-α production by monocytes in Ca2+ free medium. This failure was total for IL-10 and partial for TNF-α. However, IL-10 and TNF-α production was fully restored following the addition of exogenous calcium. Accordingly, addition of BAPTA-AM and cyclosporine-A, fully and partially inhibited IL-10 and TNF-α respectively. The PKA pathway was crucial for IL-10 production but only partially involved in gp120-induced TNF-α. The PLC pathway was partially and equivalently involved in gp120-induced TNF-α and IL-10. Moreover, the inhibition of PI3K, ERK1/2, p38 MAP-kinases and NF-κB pathways totally abolished the production of both cytokines. In conclusion, this study revealed the crucial calcium signaling pathway triggered by HIV-1 gp120 to control the production of these two cytokines: TNF-α and IL-10. The finding could help in the development of a new therapeutic strategy to alleviate the chronic hyper-immune-activation observed in HIV-1 infected patients.

PMID:
30464243
PMCID:
PMC6249280
DOI:
10.1038/s41598-018-35478-1
[Indexed for MEDLINE]
Free PMC Article

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