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J Infect Dis. 2014 Nov 15;210(10):1562-72. doi: 10.1093/infdis/jiu317. Epub 2014 Jun 5.

Antigen-presenting phagocytic cells ingest malaria parasites and increase HIV replication in a tumor necrosis factor α-dependent manner.

Author information

1
University of California-San Diego, La Jolla Seattle Biomedical Research Institute, Washington.
2
University of California-San Diego, La Jolla.
3
Seattle Biomedical Research Institute, Washington.
4
Seattle Biomedical Research Institute, Washington National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland.

Abstract

BACKGROUND:

Plasmodium falciparum infection induces human immunodeficiency virus (HIV) replication and accelerates a decline in CD4(+) T-cell count. The mechanisms contributing to these interactions have not been fully elucidated.

METHODS:

We infected peripheral blood mononuclear cells (PBMCs) with HIV type 1 (HIV-1) and then cocultured them with P. falciparum-infected red blood cells (iRBCs) or uninfected RBCs (uRBCs). Levels of HIV-1 p24 antigen and activation-associated cytokines were measured in culture supernatants. T-cell surface activation was assessed by flow cytometry.

RESULTS:

It has been reported that iRBCs increase HIV replication, compared with uRBCs; that neutralizing tumor necrosis factor α (TNF-α) abrogates this increase; and that hemozoin enhances HIV production. In this study, we confirmed that TNF-α plays an important role in this interaction. We show that iRBCs increased CD4(+) T-cell expression of HLA-DR(+)/CD38(+) (P = .001), that monocyte/macrophage depletion reduced HIV production by 40%-50% (P < .001), and that hemozoin-laden monocytes/macrophages that were preincubated with iRBCs also stimulated HIV production.

CONCLUSIONS:

iRBCs activate CD4(+) T cells and stimulate HIV replication in a TNF-α-dependent manner following malarial antigen processing by monocytes/macrophages. These results suggest that the persistent elevation of HIV replication during and after acute bouts of P. falciparum malaria may be due, at least in part, to ongoing stimulation of CD4(+) T cells by hemozoin-loaded antigen-presenting cells within lymphoid tissues.

KEYWORDS:

HIV; P. falciparum; co-infection; interaction; malaria; mechanism of increased viral load

PMID:
24903666
PMCID:
PMC4215075
DOI:
10.1093/infdis/jiu317
[Indexed for MEDLINE]
Free PMC Article

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