Differential modulation of CCR5-tropic human immunodeficiency virus-1 transfer from macrophages towards T cells under interleukin-4/interleukin-13 microenvironment.
Macrophages constitute major human immunodeficiency virus type 1 (HIV-1) reservoirs at the mucosal level, and their functional activity is modulated by cytokine environments that could play a role in HIV-1 mucosal spread. As proof of concept, we herein evaluated the modulation of HIV/macrophages interactions associated with two ubiquitous T(h)2 cytokines, namely, interleukin (IL)-4 and IL-13, using the in vitro model of R5-HIV-1 transfer from macrophages to T lymphocytes. Monocyte-derived macrophages differentiated in the presence of IL-4 (M-4) transferred the virus to T cells more efficiently than those differentiated in the presence of interleukin-13 (M-13), likely because to their high capacity to capture and produce HIV-1 and to recruit HIV-1 target T cell. However, M-13 harbored high levels of HIV DNA, similarly to M-4, and secreted HIV-activating factors. Notably, uninfected macrophages recruited HIV-1 target T cells (CCR4(+)IL-13(+) T(h)2 cells and CD4(+)CCR5(+) T cells), indicating their role in facilitating the HIV-1 spread by a passive manner. Strikingly, R5-HIV-1 reprogrammed macrophages toward a T(h)1 secretion pattern. Thus, T(h)2 microenvironment facilitates the emergence of HIV-1 macrophage reservoir and HIV-1 spread. In conclusion, secreted cytokines within mucosae may differentially influence both the HIV-1 production within the mucosal target cells reservoir and its spread thorough the mucosal tissue.
Saïdi
Héla
H
Unité INSERM Internationale U743 Immunologie Humaine, Equipe Immunité et Biothérapie Muqueuse, Centre de Recherches Biomédicales des Cordeliers, Paris, France. hela.saidi@pasteur.fr
Carbonneil
Cédric
C
Magri
Giuliana
G
Eslahpazir
Jobin
J
Sekaly
Rafick-Pierre
RP
Bélec
Laurent
L
D002454:Cell Differentiation; D002478:Cells, Cultured; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D018793:Interleukin-13 / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000821:virology*; D019713:Receptors, CCR5 / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology*
D018793:Interleukin-13; D019713:Receptors, CCR5; D015847:Interleukin-4