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.

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.