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Fibronectin shedding by Leishmania may influence the parasite-macrophage interaction
M A Vannier-Santos1, E M Saraiva, A Martiny
1Departamento de Parasitologia e Biofísica Celular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brasil.
Abstract:
Fibronectin (FN) is a large extracellular matrix protein involved in the endocytosis of several types of particles by different phagocytes. Here we investigated the role of FN in the entry and destruction of Leishmania amazonensis promastigotes (flagellated form) by murine resident peritoneal macrophages. We also studied the lateral mobility of this protein on the surface of the parasite cells using a immunogold technique. We compared the effects of addition and depletion of FN on infective and non-infective populations of Leishmania promastigotes. The invasion by the latter but not by the former, was increased by FN, and the uptake of these cells was more sensitive to FN depletion from the culture medium. We also observed enhanced killing of intracellular infective promastigotes upon FN addition to the macrophage cultures. Immunocytochemical localization of FN on the surface of the flagellates revealed that the parasite cells released bound FN by membrane shedding in a constitutive fashion. Therefore we conclude that FN removal by shedding may be part of a physiological mechanism by which the parasites evade intracellular destruction by host cells.
Insights
Fibronectin (FN) aids Leishmania parasite entry into macrophages but parasites shed FN to evade destruction. This extracellular matrix protein plays a dual role in parasite-host interactions.
Area of Science:
- Immunology
- Cell Biology
- Parasitology
Background:
- Fibronectin (FN) is an extracellular matrix protein crucial for phagocytosis by macrophages.
- Leishmania amazonensis is an important human pathogen causing leishmaniasis.
- Understanding parasite-host interactions is key to developing new therapies.
Purpose of the Study:
- To investigate the role of fibronectin in the uptake and destruction of Leishmania amazonensis by macrophages.
- To examine the dynamics of fibronectin on the parasite surface.
Main Methods:
- Murine resident peritoneal macrophages were used to study Leishmania amazonensis entry.
- Fibronectin levels were manipulated (addition/depletion) in cell cultures.
- Immunogold technique and immunocytochemistry were employed to localize fibronectin.
Main Results:
- Fibronectin enhanced the invasion of non-infective Leishmania promastigotes but not infective forms.
- Macrophage uptake of non-infective promastigotes was sensitive to fibronectin depletion.
- Addition of fibronectin increased the killing of intracellular infective promastigotes.
- Leishmania parasites constitutively shed fibronectin from their surface via membrane shedding.
Conclusions:
- Fibronectin plays a differential role in Leishmania invasion depending on parasite infectivity.
- Parasite-induced fibronectin shedding is a potential mechanism to evade host cell-mediated destruction.
- Targeting fibronectin-parasite interactions could offer new strategies against leishmaniasis.