Over-production of BAFF by dendritic cells and inflammatory monocytes during primary HIV-1 infection.
Gwenoline
Borhis1, 2,
Nada
Chaoul3,
Caroline
Gilbert4,
Christophe
Gras5,
Cécile
Goujard6, 7,
Laurence
Meyer8,
Stéphane
Paul9,
Henia
Saoudin9,
Jean-Philippe
Herbeuval5 and
Yolande
Richard1, 2*
-
1
INSERM U1016, CNRS UMR8104, Infection Immunity and Inflammation Department, France
-
2
Université Paris Descartes, France
-
3
CEA, DSV/ iMETI, France
-
4
Université Laval, Centre de recherche du CHU de Quebec, Canada
-
5
CNRS UMR8603, France
-
6
INSERM U802, France
-
7
AP-HP, France
-
8
INSERM U1018, France
-
9
GIMAP EA3064, France
Recent studies indicate that early activation of the immune system bears a major role in shaping B-cell repertoire and virus-specific antibody (Ab) response during primary HIV-1/SIV infection. The B cell–activating factor belonging to the TNF family (BAFF) is an inflammatory cytokine involved in Ab response and Ig class switching. However, BAFF excess also promotes the abnormal survival of self-reactive B-cell clones. We have thus evaluated the potential contribution of BAFF/APRIL impaired B-cell responses in 35 untreated primary HIV-1-infected patients (PHI) (PRIMO-ANRS Co06). Serum BAFF levels were strongly increased at enrolment, which occurs between 20 and 45 days post-infection (pi), and rapidly decreased after one month. At six months pi, the average BAFF level was similar to that of healthy donors in most patients. BAFF levels correlate directly with plasma viral load and inversely with CD4+ T-cell counts. Moreover, human monocytes and myeloid dendritic cells released BAFF when exposed in vitro to R5 HIV-1, TLR3 agonist or type I IFN. Plasmacytoid dendritic cells were unable to secrete BAFF but exhibited its enhanced membrane expression in response to HIV-1 and CpG. However, preliminary data indicated that blood CD16+ monocytes might be a major source of BAFF in PHI patients. Altogether, our data suggest that HIV-1 triggers BAFF over-production by dendritic cells and inflammatory monocytes, which likely contributes to local inflammation after their rapid relocation in various tissues, including gut mucosa. BAFF over-production might thus contribute to early inflammation and to the imbalance between polyclonal and virus-specific Ab responses.
Keywords:
B cells,
HIV-1,
BAFF,
acute infection,
Monocytes,
Dendritic Cells
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Borhis
G,
Chaoul
N,
Gilbert
C,
Gras
C,
Goujard
C,
Meyer
L,
Paul
S,
Saoudin
H,
Herbeuval
J and
Richard
Y
(2013). Over-production of BAFF by dendritic cells and inflammatory monocytes during primary HIV-1 infection..
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00453
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Received:
10 Apr 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Yolande Richard, INSERM U1016, CNRS UMR8104, Infection Immunity and Inflammation Department, Paris, France, yolande.richard@inserm.fr