title: Differential partial activation phenotype and production of tumour necrosis factor-α by conventional dendritic cells in response to lipopolysaccharide in HIV+ viraemic subjects and HIV+ controllers.
abstract: HIV(+) subjects are reported to have increased soluble CD14 (sCD14) in plasma, an indicator of microbial translocation. We evaluated if microbial translocation has a differential impact on the activation and function of conventional dendritic cells (cDC) from viraemic HIV(+) subjects and HIV(+) controllers (CTs). The HIV(+) subjects were classified into two groups according to their plasma viral load (pVL): CT and viraemic. Subjects without HIV were included as controls (HIV(-) ). The frequencies and phenotypes of cDC from these subjects were evaluated by multi-parameter flow cytometry. In addition, peripheral blood mononuclear cells (PBMCs) were stimulated with lipopolysaccharide (LPS) or single-stranded RNA40 (ssRNA40), the phenotype of the cDC and the intracellular production of tumour necrosis factor (TNF)-α by the cDC were evaluated by flow cytometry. We observed a partial activation phenotype for the cDC in the viraemic subjects and CTs ex vivo and after LPS activation, which showed differences in the expression of CD40 and CD86. Furthermore, in response to LPS the cDC from the viraemic subjects produced more TNF-α compared to the cDC from CTs. Interestingly, the percentage of TNF-α(+) cDC was found to be correlated positively with the pVL. The partial activation of cDC and the over-production of TNF-α in response to LPS in viraemic HIV(+) subjects might be related to the increased chronic activation observed in these subjects. In contrast, cDC from CTs seem to have a regulated response to LPS, indicating that they respond differently to chronic immune activation. These results may have implications in the development of HIV therapies and vaccines using DC.
authors.affiliation: Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, 'Ismael Cosio Villegas', México, DF, México; Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades, Centro Médico Nacional 'Siglo XXI', México, DF, México.
authors.forename: R
authors.initials: R
authors.lastname: Camacho-Sandoval
authors.forename: P M
authors.initials: PM
authors.lastname: Del Río Estrada
authors.forename: A
authors.initials: A
authors.lastname: Rivero-Arrieta
authors.forename: G
authors.initials: G
authors.lastname: Reyes-Terán
authors.forename: L C
authors.initials: LC
authors.lastname: Bonifaz
mesh_terms: D000328:Adult; D000368:Aged; D051940:B7-2 Antigen / Q000032:analysis; D018791:CD4 Lymphocyte Count; D019013:CD40 Antigens / Q000032:analysis; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014766:Viremia / Q000276:immunology*
chemical_list: D051940:B7-2 Antigen; D019013:CD40 Antigens; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha
keywords: HIV+ controllers (CTs); TNF-α; conventional dendritic cells (cDC); microbial translocation