HIV-1 exposed dendritic cells show increased... : AIDS (original) (raw)

Basic Science: Original Papers

HIV-1 exposed dendritic cells show increased pro-inflammatory cytokine production but reduced IL-1ra following lipopolysaccharide stimulation

Loré, Karinab; Sönnerborg, Andersa,b; Olsson, Jennyb; Patterson, Bruce K.d; Fehniger, Thomas E.b; Perbeck, Leifc; Andersson, Janb

From the Department of Immunology, Microbiology, Pathology and Infectious Diseases, Karolinska Institute, the aDivision of Clinical Virology, the bDivision of Infectious Diseases and the cDepartment of Surgery, Huddinge University Hospital, Huddinge, Stockholm, Sweden, and the dDepartment of Obstetrics and Gynecology, Northwestern University Medical School, Chicago, Illinois, USA.

Sponsorship: This study was supported by Medical Research Council (grant 9082 and 10850), NIH (grant A141536-02) and Swedish Physicians against Aids Research Fund.

Correspondence to: Karin Loré, Division of Clinical Virology, Karolinska institute, F68, Huddinge University Hospital, S-141 86 Huddinge, Sweden. E-mail: [email protected]

Received: 6 January 1999; revised: 23 June 1999; accepted: 5 July 1999.

Abstract

Objectives:

Dendritic cells (DC) are potential first target cells in sexually transmitted HIV-1 infection. They are also considered to be central in the activation of naive T cells, which thereupon can become permissive for HIV-1. In addition, activated DC express effector molecules, which likely contribute to the direction of T helper (Th1/Th2)-specific immune responses.

Methods:

The capacity of cytokine and chemokine production in in vitro DC infected and uninfected with HIV-1 was assessed by enzyme-linked immunosorbent assay (ELISA) and by in situ immunocytochemical detection at the single cell level. Fluorescent in situ 5‚-nuclease assay (FISNA) was used for quantitative evaluation of HIV-1 _gag-_positive cells.

Results:

Macrophage-tropic HIV-1 effectively infected 20-40% of in vitro cultured DC. However, this activity alone did not induce detectable cytokine or chemokine protein expression in DC. In contrast, lipopolysaccharide (LPS) stimulation of these HIV-1-infected DC resulted in a significantly increased level of cells producing tumour necrosis factor agr; (TNF-agr;) and interleukin (IL) 1β but reduced frequencies of cells producing IL-1 receptor antagonist (IL-1ra) compared with the LPS-stimulated but uninfected DC cultures (P<0.05). Furthermore, an extensive production of the β-chemokines [RANTES, macrophage inflammatory proteins (MIP) 1agr;? and 1β] was detected in DC in response to both LPS and HIV-1 plus LPS.

Conclusions:

These findings indicate that HIV-1 infected DC may have an increased proinflammatory activity. Elevated production of cytokines such as TNF-agr; and IL-1β and reduced IL-1ra may contribute to enhanced replication of HIV-1 in bystander T cells. Gram-negative bacterial infection and gut-associated bacterial translocation in HIV-1-infected individuals may also result in endotoxin-mediated reactivation of HIV-1 in bystander CD4 CD45RO T cells caused by the increased production of proinflammatory cytokines in DC.