Nerve growth factor stimulation promotes CXCL-12 attraction of monocytes but decreases human immunodeficiency virus replication in attracted population.
The neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) are key molecules in the central nervous system development, which also exert specific effects on cells of the immune system. With regard to the latter, in vitro as well as in vivo data suggested that neurotrophins may play a role in human immunodeficiency virus (HIV) infection, especially in perivascular spaces where infiltrated macrophages express NGF. In the present study, we examined the expression of neurotrophins and their receptors in human monocyte-derived macrophages (MDMs) during infection by the R5 prototype HIV1/Ba-L strain. We then assessed to what extent neurotrophins themselves modulate infected macrophage survival and the level of virus production. The data show that neurotrophins and neurotrophin receptors are not modulated during HIV replication. Likewise, exogenous neurotrophins, or alternatively the blocking of neurotrophin receptors, neither modulated MDM sensitivity to HIV infection and replication nor altered their viability. In contrast, NGF clearly increased CD184 expression in macrophages, but this did not sensitize them to the X4 isolate HIV-1/Lai infection. Nevertheless, NGF enhanced monocyte chemotactic response to low CXCL-12 concentration regardless of infection. Surprisingly, CXCL-12-attracted monocytes from NGF-stimulated, HIV-infected cultures produced decreased amounts of virus progeny than their non-NGF-stimulated counterparts. This suggests a preferential effect on uninfected monocytes. Together these findings suggest a role for NGF in the continuous attraction of activated monocytes to the perivascular spaces, contributing to the chronic inflammatory state rather than neuroinvasion by HIV.
Samah
Boubekeur
B
Institute of Emerging Diseases and Innovative Therapies, Division of ImmunoVirology, CEA, 18 route du Panorama, Fontenay-aux Roses, France.
Porcheray
Fabrice
F
Dereuddre-Bosquet
Nathalie
N
Gras
Gabriel
G
D054377:Chemokine CXCL12 / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D015536:Down-Regulation; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D020932:Nerve Growth Factor / Q000494:pharmacology / Q000502:physiology*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D054377:Chemokine CXCL12; D017475:Receptors, Nerve Growth Factor; D020932:Nerve Growth Factor