Opsonization modulates Rac-1 activation during cell entry by Leishmania amazonensis.
Lesions caused by Leishmania amazonensis normally heal, but relapses occur due to parasite persistence in host tissues. It has been proposed that infection of fibroblasts plays an important role in this process by providing the parasites with a safe haven in which to replicate. However, most previous studies have focused on the entry of Leishmania into macrophages, a process mediated by serum opsonins. To gain insight into a possible role of nonopsonic entry in the intracellular persistence of amastigotes, we examined the invasion of Chinese hamster ovary (CHO) cells. Amastigotes entered CHO cells by a cytochalasin D, genistein, wortmannin, and 2,3-butanedione monoxime-sensitive pathway and replicated within phagolysosomes. However, unlike most phagocytic processes described to date, amastigote internalization in CHO cells involved activation of the GTPases Rho and Cdc42 but not Rac-1. When uptake was mediated by fibronectin or when amastigotes were opsonized with immunoglobulin G and internalized by Fc receptor-expressing CHO cells, Rac-1 activation was restored and found to be required for parasite internalization. Given the essential role of Rac in assembly of the respiratory burst oxidase, invasion through this nonopsonic, Rac-1-independent pathway may play a central role in the intracellular survival of Leishmania in immune hosts.
Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut 06536, USA.
J
J
Morehead
I
I
Coppens
N W
NW
Andrews
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D016466:CHO Cells; D006224:Cricetinae; D004789:Enzyme Activation; D005353:Fibronectins / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007894:Leishmania mexicana / Q000276:immunology*; D008247:Lysosomes / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D009895:Opsonin Proteins / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D020764:cdc42 GTP-Binding Protein / Q000276:immunology; D020830:rac1 GTP-Binding Protein / Q000276:immunology*
D000913:Antibodies, Protozoan; D005353:Fibronectins; D007074:Immunoglobulin G; D009895:Opsonin Proteins; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein