Dendritic cells derived from hemozoin-loaded monocytes display a partial maturation phenotype that promotes HIV-1 trans-infection of CD4+ T cells and virus replication.
Coinfection of HIV-1 patients with Plasmodium falciparum, the etiological agent of malaria, results in a raise of viral load and an acceleration of disease progression. The primary objective of this study was to investigate whether the malarial pigment hemozoin (HZ), a heme by-product of hemoglobin digestion by malaria parasites, can affect HIV-1 transmission by monocytes-derived dendritic cells (DCs) to CD4(+) T cells when HZ is initially internalized in monocytes before their differentiation in DCs. We demonstrate in this study that HZ treatment during the differentiation process induces an intermediate maturation phenotype when compared with immature and fully mature DCs. Furthermore, the DC-mediated transfer of HIV-1 is enhanced in presence of HZ, a phenomenon that may be linked with the capacity of HZ-loaded cells to interact and activate CD4(+) T cells. Altogether our findings suggest a new mechanism that could partially explain the increased HIV-1 virus production during a coinfection with P. falciparum. Understanding the multifaceted interactions between P. falciparum and HIV-1 is an important challenge that could lead to the development of new treatment strategies.
Diou
Juliette
J
Centre de Recherche en Infectiologie, Centre Hospitalier de l'Université Laval and Faculté de Médecine, Université Laval, Québec City, Québec, Canada.
Tardif
Mélanie R
MR
Barat
Corinne
C
Tremblay
Michel J
MJ
D000962:Antimalarials / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology*; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000469:parasitology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology; D006420:Hemeproteins / Q000494:pharmacology*; D006801:Humans; D016130:Immunophenotyping; D016778:Malaria, Falciparum / Q000276:immunology / Q000473:pathology / Q000821:virology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000473:pathology / Q000821:virology*; D010860:Pigments, Biological / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects* / Q000276:immunology
D000962:Antimalarials; D006420:Hemeproteins; D010860:Pigments, Biological; C020753:hemozoin