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Blood, 15 October 2000, Vol. 96, No. 8, pp. 2649-2654
PLENARY PAPER
Up-regulation of HIV coreceptors CXCR4 and CCR5 on
CD4+ T cells during human endotoxemia and after
stimulation with (myco)bacterial antigens: the role of
cytokines
Nicole P. Juffermans,
William A. Paxton,
Pascale E. P. Dekkers,
Annelies Verbon,
Evert de
Jonge,
Peter Speelman,
Sander J. H. van Deventer, and
Tom van der Poll
From the Laboratory of Experimental Internal Medicine,
the Department of Internal Medicine, Division of Infectious Diseases,
Tropical Medicine and AIDS, the Department of Human Retrovirology, the
Department of Intensive Care Medicine, Academic Medical Center,
University of Amsterdam, Amsterdam, the Netherlands.
Concurrent infections in patients with human immunodeficiency virus
(HIV) infection stimulate HIV replication. Chemokine receptors CXCR4
and CCR5 can act as HIV coreceptors. The authors hypothesized that
concurrent infection increases the HIV load through up-regulation of
CXCR4 and CCR5. Using experimental endotoxemia as a model of infection,
changes in HIV coreceptor expression were assessed in 8 subjects
injected with lipopolysaccharide (LPS, 4 ng/kg). The expression of
CXCR4 and CCR5 on CD4+ T cells was increased 2- to 4-fold,
4 to 6 hours after LPS injection. In whole blood in vitro, LPS induced
a time- and dose-dependent increase in the expression of
CXCR4 and CCR5 on CD4+ T cells. Similar changes were
observed after stimulation with cell wall components of
Mycobacterium tuberculosis (lipoarabinnomannan) or
Staphylococcus aureus (lipoteichoic acid), or
with staphylococcal enterotoxin B. LPS increased viral infectivity of
CD4-enriched peripheral blood mononuclear cells (PBMCs) with a T-tropic
HIV strain. In contrast, M-tropic virus infectivity was reduced,
possibly because of elevated levels of the CCR5 ligand cytokines RANTES and MIP-1 . LPS-stimulated up-regulation of CXCR4 and CCR5 in vitro
was inhibited by anti-TNF and anti-IFN . Incubation with recombinant
TNF or IFN mimicked the LPS effect. Anti-interleukin 10 (anti-IL-10) reduced CCR5 expression, without influencing CXCR4. In
accordance, rIL-10 induced up-regulation of CCR5, but not of CXCR4.
Intercurrent infections during HIV infection may up-regulate CXCR4 and
CCR5 on CD4+ T cells, at least in part via the action of
cytokines. Such infections may favor selectivity of HIV for
CD4+ T cells expressing CXCR4.

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