title: Plasmacytoid dendritic cells and myeloid cells differently contribute to B-cell-activating factor belonging to the tumor necrosis factor superfamily overexpression during primary HIV infection.
abstract: BACKGROUND
  After describing heightened levels of circulating B-cell-activating factor belonging to the tumor necrosis factor superfamily (BAFF) as well as changes in B-cell phenotype and functions during acute infection by simian immunodeficiency virus, we wanted to determine whether and by which cells BAFF was over-expressed in primary HIV-infected (PHI) patients.
  
  
  METHODS
  We simultaneously examined circulating BAFF levels by ELISA and membrane-bound BAFF (mBAFF) expression by flow cytometry in peripheral blood mononuclear cells of healthy donors and PHI patients followed for 6 months. We also examined whether HIV-1 modifies BAFF expression or release in various myeloid cells and plasmacytoid dendritic cells (pDC) in vitro.
  
  
  RESULTS
  Circulating BAFF levels were transiently increased at enrolment. They positively correlated with CXCL10 levels and inversely with B-cell counts. Whereas mBAFF was expressed by most pDC and on a fraction of intermediate monocytes in healthy donors, the frequency of mBAFF cells significantly increased among nonclassical monocytes and CD1c dendritic cells but decreased among pDC in PHI patients. In contrast to myeloid cells, pDC never released BAFF upon stimulation. Their mBAFF expression was enhanced by HIV-1, independently of type I IFN.
  
  
  CONCLUSIONS
  Our findings reveal that the pattern of BAFF expression by myeloid cells and pDC is altered in PHI patients and constitutes a valuable marker of immune activation whose circulating levels correlate with CXCL10 levels. Due to their homing in different tissue areas, pDC and myeloid cells might target different B-cell subsets through their mBAFF expression or soluble BAFF release.
authors.affiliation: aINSERMu1016, Institut CochinbCNRS-UMR8104cUniversité Paris Descartes, Sorbonne Paris Cité, ParisdService d'Immuno-Virologie, CEA/DSV/ iMETI, Fontenay-aux-RoseseCBNIT, CNRS-UMR8601, Faculté des Saints-Pères, ParisfINSERM UMRS1018gAssistance Publique-Hôpitaux de Paris, Service d'épidémiologie et de santé publique, Hôpital BicêtrehUniversité Paris-Sud, Le Kremlin-BicêtreiGIMAP EA3064, Universités de Lyon et Jean Monnet de St-Etienne, St EtiennejAssistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, FrancekUniversité Laval, Centre de recherche du CHU de Québec, Québec G1V 4G2, Canada.*Chantal Burelout and Nada Chaoul contributed equally to the experimental work and writing of this article.
authors.forename: Gwenoline
authors.initials: G
authors.lastname: Borhis
authors.forename: Chantal
authors.initials: C
authors.lastname: Burelout
authors.forename: Nada
authors.initials: N
authors.lastname: Chaoul
authors.forename: Nikaïa
authors.initials: N
authors.lastname: Smith
authors.forename: Cecile
authors.initials: C
authors.lastname: Goujard
authors.forename: Laurence
authors.initials: L
authors.lastname: Meyer
authors.forename: Stephane
authors.initials: S
authors.lastname: Paul
authors.forename: Henia
authors.initials: H
authors.lastname: Saoudin
authors.forename: Anne
authors.initials: A
authors.lastname: Hosmalin
authors.forename: Caroline
authors.initials: C
authors.lastname: Gilbert
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Herbeuval
authors.forename: Yolande
authors.initials: Y
authors.lastname: Richard
mesh_terms: D000328:Adult; D000368:Aged; D053264:B-Cell Activating Factor / Q000096:biosynthesis* / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology*; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D053264:B-Cell Activating Factor