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In Vivo Infection with Leishmania amazonensis to Evaluate Parasite Virulence in Mice
Published on: February 20, 2020
Extracellular matrix alterations in experimental murine Leishmania (L.) amazonensis infection
A L Abreu-Silva1, K S Calabrese, R A Mortara
1Departamento de Patologia da Universidade Estadual do Maranhão, São Luís, Maranhão, Brasil.
Abstract:
Here we describe extracellular matrix alterations in footpad lesions and draining lymph nodes caused by Leishmania (L.) amazonensis in mouse strains with distinct susceptibilities to this parasite: BALB/c (susceptible), C57BL/6 (intermediate), and DBA/2 (resistant). Changes in ECM were observed mainly in BALB/c mice that, in general, presented tissue damage associated with high parasite burden. Under polarized light, Sirius Red revealed type I collagen that was predominant in the primary lesion in all strains studied at the early phase of infection, but gradually decreased and was replaced by abundant type III collagen fibres in chronic phase lesions. The presence of type III collagen seemed to provide support to inflammatory cells, mainly vacuolated and parasitized macrophages. Laminin expression was not altered during infection by L. (L.) amazonensis in any of the mouse strains studied. Furthermore, the decreased fibronectin expression, in all strains, in areas where amastigotes have been found, indicated that this decline was also not related to the genetic background.
Insights
Extracellular matrix changes in Leishmania amazonensis infections reveal type III collagen supports parasitized macrophages in susceptible mice. Fibronectin and laminin expression remained largely unaffected by parasite burden or genetic background.
Area of Science:
- Immunology
- Parasitology
- Biochemistry
Background:
- Leishmania (L.) amazonensis causes visceral and cutaneous leishmaniasis.
- Extracellular matrix (ECM) plays a crucial role in tissue structure and immune cell function.
- Understanding ECM alterations during infection is vital for developing effective treatments.
Purpose of the Study:
- To investigate ECM modifications in footpad lesions and lymph nodes of mice with varying susceptibility to Leishmania (L.) amazonensis.
- To correlate ECM changes with parasite burden and host genetic background.
Main Methods:
- Comparative analysis of ECM components (collagens, fibronectin, laminin) in susceptible (BALB/c), intermediate (C57BL/6), and resistant (DBA/2) mouse strains.
- Histological examination of footpad lesions and draining lymph nodes using Sirius Red staining and polarized light microscopy.
- Assessment of protein expression levels via immunohistochemistry.
Main Results:
- Significant ECM alterations were primarily observed in susceptible BALB/c mice with high parasite loads and tissue damage.
- Type I collagen predominated in early lesions across all strains, gradually replaced by type III collagen in chronic lesions.
- Type III collagen appeared to support inflammatory cells, particularly parasitized macrophages.
- Fibronectin expression decreased in infected areas, irrespective of mouse strain.
- Laminin expression remained unchanged throughout the infection.
Conclusions:
- Leishmania (L.) amazonensis infection induces significant ECM remodeling, particularly in susceptible hosts.
- The shift from type I to type III collagen during chronic infection may influence the inflammatory microenvironment.
- ECM changes, specifically fibronectin and laminin, are not solely dictated by host genetic susceptibility.
- Further research into ECM's role could offer novel therapeutic targets for leishmaniasis.
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