title: Antigen-presenting phagocytic cells ingest malaria parasites and increase HIV replication in a tumor necrosis factor α-dependent manner.
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.
authors.affiliation: University of California-San Diego, La Jolla Seattle Biomedical Research Institute, Washington.
authors.forename: Marika
authors.initials: M
authors.lastname: Orlov
authors.affiliation: University of California-San Diego, La Jolla.
authors.forename: Florin
authors.initials: F
authors.lastname: Vaida
authors.affiliation: Seattle Biomedical Research Institute, Washington.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Williamson
authors.affiliation: University of California-San Diego, La Jolla.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Deng
authors.affiliation: University of California-San Diego, La Jolla.
authors.forename: David M
authors.initials: DM
authors.lastname: Smith
authors.affiliation: Seattle Biomedical Research Institute, Washington National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland.
authors.forename: Patrick E
authors.initials: PE
authors.lastname: Duffy
authors.affiliation: University of California-San Diego, La Jolla.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Schooley
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology*; D018920:Coculture Techniques; D003470:Culture Media / Q000737:chemistry; D016207:Cytokines / Q000032:analysis; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D010586:Phagocytes / Q000276:immunology*; D010587:Phagocytosis; D010963:Plasmodium falciparum / Q000276:immunology*; D014779:Virus Replication
chemical_list: D003470:Culture Media; D016207:Cytokines; D016655:HIV Core Protein p24
keywords: HIV; P. falciparum; co-infection; interaction; malaria; mechanism of increased viral load