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.
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-1beta. LPS-stimulated up-regulation of CXCR4 and CCR5 in vitro was inhibited by anti-TNF and anti-IFN gamma. Incubation with recombinant TNF or IFN gamma 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. (Blood. 2000;96:2649-2654)
Juffermans
N P
NP
Laboratory of Experimental Internal Medicine, University of Amsterdam, The Netherlands.
Paxton
W A
WA
Dekkers
P E
PE
Verbon
A
A
de Jonge
E
E
Speelman
P
P
van Deventer
S J
SJ
van der Poll
T
T
D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D001424:Bacterial Infections / Q000150:complications* / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D002473:Cell Wall / Q000737:chemistry; D002478:Cells, Cultured; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000502:physiology; D019446:Endotoxemia / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D004768:Enterotoxins / Q000276:immunology* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D015658:HIV Infections / Q000150:complications* / Q000821:virology; D018023:HIV Seronegativity; D015497:HIV-1 / Q000145:classification / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000502:physiology; D008954:Models, Biological; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D019713:Receptors, CCR5 / Q000096:biosynthesis* / Q000235:genetics; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D012641:Selection, Genetic; D013211:Staphylococcus aureus / Q000276:immunology*; D013682:Teichoic Acids / Q000276:immunology* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology; D014779:Virus Replication
D000942:Antigens, Bacterial; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D004768:Enterotoxins; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D011994:Recombinant Proteins; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; C050016:lipoarabinomannan; D016753:Interleukin-10; C031818:enterotoxin B, staphylococcal; C009900:lipoteichoic acid; D007371:Interferon-gamma