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Published on: January 27, 2019
Peripheral macrophage depletion reduces central nervous system parasitism and damage in Trypanosoma cruzi-infected
Grace C Silva1, Patrícia R A Nagib, Egler Chiari
1Department of Morphology, Federal University of Minas Gerais, Av. Antonio Carlos, 6627, 31270.901 Belo Horizonte, Minas Gerais, Brazil.
Abstract:
We aim at investigating the role of blood born macrophages on the brain reaction to Trypanosoma cruzi infection in suckling rats. This infection provoked the appearance of numerous ED1(+) cells in the neural parenchyma and increased the amount of meningeal and perivascular ED2(+) macrophages. CD8(+) and NKR(+) cells also occurred. Parenchymal blood vessels showed strong ICAM-1 and decreased occludin immunoreactivities. Selective depletion of peripheral macrophages by clodronate liposomes decreased tissue parasitism, nodular lesions, ICAM-1 upregulation and leukocyte infiltration. Occludin immunoreactivity remained as in uninfected animals. Our results indicate a role for blood-born macrophages in both parasite invasion and brain reaction. Microglia activation cannot be discarded.
Insights
Blood-born macrophages play a key role in Trypanosoma cruzi brain infections in rats. Depleting these macrophages reduced parasite invasion and brain inflammation, suggesting a therapeutic target.
Area of Science:
- Neuroimmunology
- Parasitology
- Infectious Diseases
Background:
- Trypanosoma cruzi infection, the causative agent of Chagas disease, can affect the central nervous system.
- The role of peripheral immune cells, particularly macrophages, in the brain's response to T. cruzi infection is not fully understood.
Purpose of the Study:
- To investigate the contribution of blood-derived macrophages to the brain's reaction during Trypanosoma cruzi infection in suckling rats.
Main Methods:
- Suckling rats were infected with Trypanosoma cruzi.
- Peripheral macrophages were selectively depleted using clodronate liposomes.
- Immunohistochemistry was used to analyze cell infiltration (ED1+, ED2+, CD8+, NKR+) and expression of ICAM-1 and occludin in brain tissue.
Main Results:
- T. cruzi infection led to increased ED1+ and ED2+ macrophage populations in the brain parenchyma, meninges, and perivascular spaces.
- Infiltration of CD8+ and NKR+ cells was observed, along with upregulated ICAM-1 and downregulated occludin in parenchymal blood vessels.
- Macrophage depletion significantly reduced parasite load, nodular lesions, ICAM-1 upregulation, and leukocyte infiltration, while preserving occludin levels.
Conclusions:
- Blood-borne macrophages are crucial mediators of parasite invasion and contribute significantly to the inflammatory brain response during Trypanosoma cruzi infection.
- Targeting peripheral macrophages may represent a viable strategy to mitigate neuroinflammation and parasite burden in T. cruzi infections.
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