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In Vivo Infection with Leishmania amazonensis to Evaluate Parasite Virulence in Mice
Published on: February 20, 2020
Leishmania amazonensis: multiple receptor-ligand interactions are involved in amastigote infection of human dendritic
Maira Cegatti Bosetto1, Selma Giorgio
1Departamento de Parasitologia, Instituto de Biologia, Universidade Estadual de Campinas, Caixa Postal 6109, Cep 13083-970, Campinas, São Paulo, Brazil.
Abstract:
In their mammalian hosts, Leishmania are obligate intracellular parasites that reside in macrophages and dendritic cells (DCs). In the present study, we have investigated in vitro the mechanisms of entry into human DCs of Leishmania amazonensis amastigotes isolated from lesions in nude mice (Am nude). The DC infection rate with Am nude was approximately 36%, while opsonization of Am nude with normal human serum and infected human serum increased the DC infection rates to 60% and 62%, respectively. Heat inactivation and depletion of antibodies in sera brought the DC infection rate down to 40%. The DC infection rate was inhibited after pre-treatment of Am nude with heparin. We were unable to implicate mannose-fucose receptors in the uptake of Am nude by DCs. Our data suggest that the ability of L. amazonensis amastigotes to infect human DCs involves the participation of at least three multiple receptor-ligand interactions, antibodies/FcR, complement components/CR and proteoglycans/heparin-binding protein.
Insights
Leishmania amazonensis amastigotes infect human dendritic cells (DCs) through multiple receptor-ligand interactions. Antibodies, complement, and proteoglycans mediate parasite entry into DCs.
Area of Science:
- Immunology
- Parasitology
- Cell Biology
Background:
- Leishmania are obligate intracellular parasites residing in macrophages and dendritic cells (DCs).
- Understanding parasite entry mechanisms into DCs is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the in vitro mechanisms of Leishmania amazonensis amastigote entry into human DCs.
- To identify the specific receptor-ligand interactions involved in parasite uptake.
Main Methods:
- Infection of human DCs with Leishmania amazonensis amastigotes (Am nude).
- Assessing infection rates with opsonized and non-opsonized parasites.
- Investigating the role of antibodies, complement, and heparin-binding proteins in parasite uptake.
Main Results:
- DC infection rate with Am nude was 36%, increasing to 60-62% with serum opsonization.
- Heat inactivation and antibody depletion reduced infection rates.
- Heparin pre-treatment inhibited DC infection.
- Mannose-fucose receptors were not implicated in Am nude uptake.
Conclusions:
- Leishmania amazonensis amastigote entry into human DCs involves multiple receptor-ligand interactions.
- Antibodies/FcR, complement components/CR, and proteoglycans/heparin-binding proteins are key mediators of parasite infection.
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