Peripheral macrophage depletion reduces central nervous system parasitism and damage in Trypanosoma cruzi-infected suckling rats

J Neuroimmunol. 2004 Apr;149(1-2):50-8. doi: 10.1016/j.jneuroim.2003.12.004.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Non-Narcotic / therapeutic use
  • Animals
  • Animals, Suckling / microbiology
  • Cell Count
  • Central Nervous System / blood supply
  • Central Nervous System / cytology
  • Central Nervous System / immunology
  • Central Nervous System / metabolism
  • Central Nervous System Parasitic Infections / pathology*
  • Chagas Disease / drug therapy*
  • Chagas Disease / metabolism
  • Clodronic Acid / therapeutic use*
  • Ectodysplasins
  • Enzyme-Linked Immunosorbent Assay / methods
  • Immunization / methods
  • Immunohistochemistry / methods
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interferon-gamma / blood
  • Leukocytes / classification
  • Leukocytes / metabolism
  • Liposomes / pharmacology
  • Macrophages / drug effects
  • Macrophages / physiology*
  • Male
  • Membrane Proteins / metabolism
  • Mice
  • Mortality
  • Occludin
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Trypanosoma cruzi*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Analgesics, Non-Narcotic
  • Ectodysplasins
  • Eda protein, mouse
  • Liposomes
  • Membrane Proteins
  • Occludin
  • Ocln protein, mouse
  • Ocln protein, rat
  • Tumor Necrosis Factor-alpha
  • Clodronic Acid
  • Intercellular Adhesion Molecule-1
  • Interferon-gamma