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Leishmania amazonensis promastigotes evade complement killing by interfering with the late steps of the cascade
A C Nunes1, F R Almeida-Campos, M F Horta
1Departamento de Bioquímica-Immunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Abstract:
During their growth in vitro, promastigotes of Leishmania amazonensis undergo differentiation from complement-susceptible to complement-resistant forms. Here, we demonstrate that both forms bind comparable amounts of C3 on their surfaces, with the predominant molecule species being the haemolytically active C3b. Likewise, equivalent amounts of C9 are deposited on both forms of promastigotes. However, while C9-bearing complexes are exposed on the cell surface of resistant promastigotes, they are cryptic in the susceptible stage of the parasites. The membrane fraction of complement-resistant promastigote lysates has the ability to inhibit complement-mediated haemolysis, blocking C9, but not C3 deposition to complement-activating complexes. Moreover, the membrane fraction of complement-resistant promastigote lysates can inhibit the late steps of guinea-pig erythrocyte lysis much more efficiently than complement-susceptible ones. Our results indicate that L. amazonensis promastigotes evade complement killing by inhibiting the cytolytic pathway of the complement cascade.
Insights
Leishmania amazonensis promastigotes evade complement killing by developing resistance. Resistant forms hide complement C9 complexes, inhibiting parasite lysis.
Area of Science:
- Immunology
- Parasitology
- Molecular Biology
Background:
- Leishmania amazonensis promastigotes differentiate in vitro from complement-susceptible to resistant forms.
- The complement system is a crucial part of innate immunity that can lyse parasites.
Purpose of the Study:
- To investigate the mechanisms by which Leishmania amazonensis promastigotes evade complement-mediated killing.
- To determine the role of complement components C3 and C9 in parasite resistance.
Main Methods:
- Comparative analysis of complement component binding (C3, C9) on susceptible and resistant promastigote forms.
- Investigation of C9-bearing complex exposure on parasite surfaces.
- Assessment of membrane fraction inhibitory activity against complement-mediated lysis.
- Evaluation of inhibition on C3 and C9 deposition.
Main Results:
- Both susceptible and resistant promastigotes bind comparable amounts of C3b.
- Equivalent C9 deposition occurs on both forms, but C9 complexes are exposed only on resistant forms.
- Membrane fractions from resistant promastigotes inhibit complement-mediated hemolysis by blocking C9 deposition and late lysis steps.
- Susceptible promastigotes show less inhibition of lysis.
Conclusions:
- Leishmania amazonensis promastigotes evade complement killing by inhibiting the terminal cytolytic pathway.
- Parasite resistance involves masking of C9-bearing complexes, preventing complement-mediated lysis.