A leucine-rich repeat motif of Leishmania parasite surface antigen 2 binds to macrophages through the complement receptor 3.
Membrane glycoconjugates on the Leishmania parasites, notably leishmanolysin and lipophosphoglycan, have been implicated in attachment and invasion of host macrophages. However, the function of parasite surface Ag 2 (PSA-2) and membrane proteophosphoglycan (PPG) has not been elucidated. In this study we demonstrate that native and recombinant Leishmania infantum PSA-2, which consists predominantly of 15 leucine-rich repeats (LRR) and a recombinant LRR domain derived from L. major PPG, bind to macrophages. The interaction is restricted to macrophages and appears to be calcium independent. We have investigated the PSA-2-macrophage interaction to identify the host receptor involved in binding and we show that binding of PSA-2 to macrophages can be blocked by Abs to the complement receptor 3 (CR3, Mac-1). Data derived from mouse macrophage studies were further confirmed using cell lines expressing human CR3, and showed that PSA-2 also binds to the human receptor. This is the first demonstration of a functional role for PSA-2. Our data indicate that in addition to leishmanolysin and lipophosphoglycan, parasite attachment and invasion of macrophages involve a third ligand comprising the LRRs shared by PSA-2 and PPG and that these interactions occur via the CR3.
Kedzierski
Lukasz
L
Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Montgomery
Jacqui
J
Bullen
Denise
D
Curtis
Joan
J
Gardiner
Elizabeth
E
Jimenez-Ruiz
Antonio
A
Handman
Emanuela
E
D020816:Amino Acid Motifs; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000953:Antigens, Protozoan / Q000276:immunology / Q000378:metabolism*; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism*; D001666:Binding Sites, Antibody; D001667:Binding, Competitive / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D018314:Leishmania infantum / Q000276:immunology*; D007930:Leucine / Q000378:metabolism*; D000090263:Leucine-Rich Repeat Proteins; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding / Q000276:immunology; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D020449:Repetitive Sequences, Amino Acid; D014162:Transfection
D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D000090263:Leucine-Rich Repeat Proteins; D016177:Macrophage-1 Antigen; D011506:Proteins; D015800:Protozoan Proteins; C072094:surface antigen P2, Leishmania; D007930:Leucine