Malaria-derived hemozoin exerts early modulatory effects on the phenotype and maturation of human dendritic cells.
Plasmodium falciparum (P. falciparum)-induced effects on the phenotype of human dendritic cells (DC) could contribute to poor induction of long-lasting protective immunity against malaria. DC ability to present antigens to naïve T cells, thus initiating adaptive immune responses depends on complex switches in chemokine receptors, production of soluble mediators and expression of molecules enabling antigen-presentation and maturation. To examine the cellular basis of these processes in the context of malaria, we performed detailed analysis of early events following exposure of human monocyte-derived DC to natural hemozoin (nHZ) and the synthetic analog of its heme core, β-hematin. DC exposed to either molecule produced high levels of the inflammatory chemokine MCP-1, showed continuous high expression of the inflammatory chemokine receptor CCR5, no upregulation of the lymphoid homing receptor CCR7 and no cytoskeletal actin redistribution with loss of podosomes. DC partially matured as indicated by increased expression of major histocompatibility complex (MHC) class II and CD86 following nHZ and β-hematin exposure, however there was a lack in expression of the maturation marker CD83 following nHZ but not β-hematin exposure. Overall our data demonstrate that exposure to nHZ partially impairs the capacity of DC to mature, an effect in part differential to β-hematin.
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Svante Arrheniusväg 20C, Stockholm, 106 91, Sweden.
Ioana
I
Bujila
Department of Oncology, University of Torino, Via Santena 5, Turin, 10126, Italy.
Evelin
E
Schwarzer
Department of Oncology, University of Torino, Via Santena 5, Turin, 10126, Italy.
Oleksii
O
Skorokhod
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Svante Arrheniusväg 20C, Stockholm, 106 91, Sweden.
Jessica M
JM
Weidner
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Svante Arrheniusväg 20C, Stockholm, 106 91, Sweden.
Marita
M
Troye-Blomberg
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Svante Arrheniusväg 20C, Stockholm, 106 91, Sweden.
Ann-Kristin
AK
Östlund Farrants
D015703:Antigens, CD / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006420:Hemeproteins / Q000494:pharmacology / Q000502:physiology*; D006790:Host-Parasite Interactions / Q000502:physiology*; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016778:Malaria, Falciparum / Q000378:metabolism* / Q000469:parasitology; D008562:Membrane Glycoproteins / Q000378:metabolism; D000069261:Podosomes / Q000187:drug effects; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D054400:Receptors, CCR7 / Q000235:genetics / Q000378:metabolism; D000097802:CD83 Antigen
D015703:Antigens, CD; D051940:B7-2 Antigen; D018932:Chemokine CCL2; D006420:Hemeproteins; D007136:Immunoglobulins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D019713:Receptors, CCR5; D054400:Receptors, CCR7; D000097802:CD83 Antigen; C111835:CCL2 protein, human; C584933:CCR5 protein, human; C515370:CCR7 protein, human; C497964:CD86 protein, human; C020753:hemozoin