CR3 (CD11b/CD18) is the major macrophage receptor for IgM antibody-mediated phagocytosis of African trypanosomes: diverse effect on subsequent synthesis of tumor necrosis factor alpha and nitric oxide.
Immunoglobulin M (IgM) antibodies to the variant surface glycoproteins (VSG) of African trypanosomes are the first and predominant class of anti-trypanosomal antibodies in the infected host. They are a major factor in controlling waves of parasitemia, but not in long-term survival. The macrophage receptor(s) that enables phagocytosis of IgM anti-VSG-coated African trypanosomes is unknown. We assessed whether complement receptor CR3 (CD11b/CD18) might be involved in mediating phagocytosis of Trypanosoma congolense. We show that murine complement C3 fragments are deposited onto T. congolense when the trypanosomes are incubated with IgM anti-VSG and fresh mouse serum. In the presence of fresh mouse serum, there is significantly and markedly less phagocytosis of IgM-opsonized T. congolense by CD11b-deficient macrophages compared to phagocytosis by wild-type macrophages (78% fewer T. congolense are ingested per macrophage). Significantly less tumor necrosis factor (TNF)-alpha (38% less), but significantly more nitric oxide (NO) (63% more) are released by CD11b-deficient macrophages that have engulfed trypanosomes than by equally treated wild-type macrophages. We conclude that CR3 is the major, but not the only, receptor involved in IgM anti-VSG-mediated phagocytosis of T. congolense by macrophages. We further conclude that IgM anti-VSG-mediated phagocytosis of T. congolense enhances synthesis of disease-producing TNF-alpha and inhibits synthesis of parasite-controlling NO. We suggest that signaling of inhibition of NO synthesis is mediated via CR3.
Pan
Wanling
W
Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK S7N 5B4, Canada.
Ogunremi
Oladele
O
Wei
Guojian
G
Shi
Meiqing
M
Tabel
Henry
H
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D039481:CD11b Antigen / Q000276:immunology / Q000378:metabolism; D018821:CD18 Antigens / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis; D014348:Trypanosoma congolense / Q000276:immunology*; D014353:Trypanosomiasis, African / Q000469:parasitology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000276:immunology
D000913:Antibodies, Protozoan; D039481:CD11b Antigen; D018821:CD18 Antigens; D007075:Immunoglobulin M; D016177:Macrophage-1 Antigen; D014409:Tumor Necrosis Factor-alpha; D014643:Variant Surface Glycoproteins, Trypanosoma; D009569:Nitric Oxide