The role of macrophage receptors in adhesion and uptake of Leishmania mexicana amastigotes.
Amastigotes of the protozoan parasite Leishmania proliferate in phagolysosomes of mammalian macrophages. Propagation of the infection is considered to occur by host-cell rupture and uptake of released parasites by uninfected macrophages. In this study, the kinetics of binding of L mexicana mexicana amastigotes to COS cells and to COS cells transfected with three different macrophage receptors (FcRII-B2, receptor for the Fc-domain of immunoglobulins; CR3, complement type 3 receptor and the mannose receptor) is compared to the rate of adhesion to peritoneal macrophages. Amastigotes isolated from macrophages cultivated in vitro bind with slow, sigmoid kinetics to COS cells expressing either of the three receptors, or to peritoneal macrophages. In contrast, amastigotes isolated from mouse lesions bind with rapid, hyperbolic kinetics to COS cells expressing the Fc receptor or to peritoneal macrophages but with slow, sigmoid kinetics to COS cells expressing the CR3 or the mannose receptor. As shown by immunofluorescence experiments, lesion-derived amastigotes contain host-derived immunoglobulins (Ig) but no complement component 3 at their surface. It is concluded that amastigotes contain no intrinsic ligand at their surface, which enables high-affinity interactions with macrophages. Opsonization by specific Ig may be of relevance in vivo because firstly, in cryosections of mouse lesions extracellular amastigotes containing surface Ig can be detected and, secondly, B cell-deficient mice reconstituted with parasite-specific Ig show a modest increase in the rate of lesion development. In addition, it is shown that amastigotes are internalized by COS cells and grow in large parasitophorous vacuoles similar to those observed in macrophages.
Peters
C
C
Max-Planck-Institut für Biologie, Abteilung Membranbiochemie, Federal Republic of Germany.
Aebischer
T
T
Stierhof
Y D
YD
Fuchs
M
M
Overath
P
P
D000268:Adhesiveness; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D002460:Cell Line; D007894:Leishmania mexicana / Q000254:growth & development* / Q000472:pathogenicity; D018655:Lymphocyte Count; D008264:Macrophages / Q000469:parasitology*; D051379:Mice; D008808:Mice, Inbred CBA; D011956:Receptors, Cell Surface / Q000502:physiology*
D011956:Receptors, Cell Surface