Ex vivo and in vitro impairment of CD36 expression and tumor necrosis factor-alpha production in human monocytes in response to Plasmodium falciparum-parasitized erythrocytes.
Severe malaria is associated with the failure of host defenses to control parasite replication, with the excessive secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), and with the sequestration of parasitized erythrocytes (PEs) in the microcirculation of vital organs. The scavenger receptor CD36, known as a major sequestration receptor, has also been identified as an important factor in mediating nonopsonic phagocytosis of PEs by monocytes and macrophages. The specific consequence of this phagocytosis is a decrease in parasite-induced TNF-alpha secretion. We evaluated the variations in CD36 level and in lipopolysaccharide (LPS)-induced TNF-alpha production in monocytes from Plasmodium falciparum-infected patients and in vitro in the presence of PEs. Both the monocytes from infected patients and from in vitro culture showed a decrease of CD36 expression and a reduced production of TNF-alpha induced by LPS. Using incubation assays with no contact between monocytes and PEs, or in the presence of a soluble supernatant obtained from the incubation of monocytes and PEs, this study shows that decreased CD36 expression was posttranscriptional and not directly related to PEs phagocytosis. In addition, these culture models suggest that the reduced capacity of TNF-alpha production occurred in 2 phases. The early phase (24 hr) appeared to be CD36 dependent and the second phase (48 hr) was due to a soluble factor produced by PEs. These observations suggest that the control of the TNF-alpha production in malaria by monocytes was not entirely dependent on the phagocytosis of PEs by CD36 and that soluble factors produced by PEs could play a role in this process.
Berry
A
A
Service de Parasitologie Mycologie, CHU Rangueil, TSA 50032, 31059 Toulouse Cedex 9, France. berry.a@chu-toulouse.fr
Chene
G
G
Benoit-Vical
F
F
Lepert
J C
JC
Bernad
J
J
Marchou
B
B
Séguéla
J P
JP
Magnaval
J F
JF
Pipy
B
B
D000818:Animals; D018955:CD36 Antigens / Q000096:biosynthesis* / Q000235:genetics; D016022:Case-Control Studies; D002478:Cells, Cultured; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology*; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D010587:Phagocytosis; D010963:Plasmodium falciparum / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D018955:CD36 Antigens; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha