HIV-1 proteins preferentially activate anti-inflammatory M2-type macrophages.
J Immunol
; 188(8): 3620-7, 2012 Apr 15.
Article
en En
| MEDLINE
| ID: mdl-22407921
ABSTRACT
HIV-1 proteins, including Tat, gp120, and Nef, activate macrophages (MΦ), which is consistent with the fact that HIV-1 infection is characterized by sustained immune activation. Meanwhile, MΦ are functionally classified into two types proinflammatory M1-MΦ and anti-inflammatory M2-MΦ. We show that HIV-1 proteins, particularly Nef, preferentially activate M2-MΦ. Extracellular Tat, gp120, and Nef activated MAPK and NF-κB pathways in human peripheral blood monocyte-derived MΦ. However, the activation was marked in M-CSF-derived M2-MΦ but not GM-CSF-derived M1-MΦ. Nef was the most potent activator, and its signaling activation was comparable to that by TNF-α. Indeed, Nef was internalized more rapidly by M2-MΦ than by M1-MΦ. The myristoylation and proline-rich motif of Nef were responsible for the observed signaling activation. Consistent with the activation of MAPK/NF-κB pathways, Nef stimulated the production of a number of proinflammatory cytokines/chemokines by M2-MΦ. However, Nef reduced the expression of CD163 and phagocytosis, the characteristic markers of M2-MΦ, indicating that Nef drives an M2-like to M1-like phenotypic shift. Because the differentiation of most tissue MΦ depends on M-CSF and its receptor, which is the essential axis for the anti-inflammatory M2-MΦ phenotype, the current study reveals an efficient mechanism by which HIV-1 proteins, such as Nef, induce the proinflammatory MΦ.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Proteína gp120 de Envoltorio del VIH
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VIH-1
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Productos del Gen tat del Virus de la Inmunodeficiencia Humana
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Productos del Gen nef del Virus de la Inmunodeficiencia Humana
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Macrófagos
Límite:
Humans
Idioma:
En
Revista:
J Immunol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Japón