Apical interactions of HIV type 1 with polarized HEC-1 cell monolayer modulate R5-HIV type 1 spread by submucosal macrophages.
The in vitro model of HIV-1 transcytosis through a monolayer of HEC-1 cells is thought to mimic the mucosal crossing of the virus that may occur in vivo. We evaluated whether the stimulation of HEC-1 by HIV may modulate HIV infection of macrophages. Thus, the ability to capture, produce, and transfer R5 viruses to T cells, attract T cells, and finally produce cytokines/chemokines, was compared between untreated macrophages (M0) and macrophages differentiated in the presence of medium collected at the basolateral pole of HEC-1, which were unstimulated [M(BL)] or stimulated with either R5-HIV-1Ba-L [M(BL-R5)] or X4-HIV-1NDK [M(BL-X4)]. M(BL-X4)-secreted CCR5-interacting chemokines integrated and replicated HIV less efficiently than did M(BL) and M(BL-R5). M(BL-R5) and M(BL-X4) similarly transmitted HIV to activated T cells. Interestingly, mannose-binding receptors and heparan sulfate proteoglycans were variously involved in HIV adsorption, whereas DC-SIGN mostly mediated the HIV transfer. Conversely to M(BL) and M(BL-X4), M(BL-R5) did not secrete eotaxin, GRO, ITAC, lymphotactin, MIP-1, MIP-3, and RANTES, which was associated with a weak capacity to recruit CD4(+)CXCR4(+)CCR5(+) T cells. In particular, M(BL-R5) specifically released soluble factors enhancing HIV production by recruited T cells. These submucosal-conditioned macrophages differentially captured, produced, and transferred R5-HIV-1 to T cells, according to the tropism of the virus deposited at the apical pole of HEC-1. These observations challenge the question of the in vivo involvement of HIV-1 as a supraepithelial stimulus that likely modulates the susceptibility for HIV-1 of submucosal target cells in favor of its transmission.
Saïdi
Héla
H
Université Paris Descartes (Paris V), Unité INSERM U743 Immunologie Humaine, Equipe Immunité et Biothérapie Muqueuse, Centre de Recherches Biomédicales des Cordeliers, Paris, France. hela.saidi@pasteur.fr
Magri
Giuliana
G
Carbonneil
Cédric
C
Bouhlal
Hicham
H
Hocini
Hakim
H
Belec
Laurent
L
D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D020895:Enterocytes / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008264:Macrophages / Q000821:virology*; D013601:T-Lymphocytes / Q000821:virology
D016207:Cytokines