RESUMEN
In view of assessing the possible contribution of dendritic cells (DCs) to HIV-related B-cell disorders, we have longitudinally measured B lymphocyte stimulator (BLyS) surface expression by myeloid DCs (mDCs) and concentrations of B-cell growth factors in the blood of subjects undergoing primary HIV infection with different rates of disease progression. We report that BLyS surface expression by mature mDCs and precursors as well as blood levels of BLyS, a proliferation-inducing ligand (APRIL), interleukin-6 (IL-6), and IL-10 increased above normal levels in both rapid and normal HIV progressors as quickly as in the acute phase of infection and persisting throughout the course of disease despite successful therapy. Consequently, hyperglobulinemia and high blood levels of circulating activated mature B cells and precursor/activated marginal zone (MZ)-like B cells were found throughout follow-up for both rapid and normal progressors. In contrast, mDC cell-surface expression of BLyS as well as blood levels of BLyS, immunoglobulin, activated mature B cells, and precursor/activated MZ-like B cells in aviremic slow progressors were similar to those observed in healthy donors. Interestingly, the levels of mature MZ B cells were significantly reduced in slow progressors. Our results suggest that DCs might modulate the outcome of the HIV-related B-cell disease progression through the expression of BLyS.
Asunto(s)
Factor Activador de Células B/metabolismo , Linfocitos B/metabolismo , Linfocitos B/patología , Células Dendríticas/metabolismo , Infecciones por VIH/metabolismo , Infecciones por VIH/patología , Adulto , Linfocitos B/inmunología , Estudios de Cohortes , Células Dendríticas/inmunología , Células Dendríticas/patología , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Infecciones por VIH/virología , VIH-1/patogenicidad , Humanos , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Masculino , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/metabolismoRESUMEN
The cytosine deaminase APOBEC3G has been identified as a host factor that inhibits HIV-1 replication. We investigated whether genetic variants of APOBEC3G that could potentially affect the protein's expression or function were associated with the risk of infection in 122 Caucasians highly exposed to HIV-1. A novel C40693T variant was significantly associated with an increased risk of infection, suggesting that there might be a role for APOBEC3G in susceptibility to HIV-1 infection that warrants further investigation.