Distinct Toll-like receptor signals regulate cerebral parasite load and interferon α/β and tumor necrosis factor α-dependent T-cell infiltration in the brains of Trypanosoma brucei-infected mice

J Infect Dis. 2012 Jan 15;205(2):320-32. doi: 10.1093/infdis/jir734. Epub 2011 Nov 23.


Background: The penetration of T cells and trypanosomes into the brain parenchyma is a major pathogenetic event in African trypanosomiasis.

Methods: The role of innate immune responses in the penetration of T cells and Trypanosoma brucei brucei into the brain was studied in knockout mice by using double immunofluorescent staining and real-time polymerase chain reaction.

Results: We demonstrate that Toll-like receptor (TLR)-MyD88-mediated signaling is required for T-cell and parasite penetration into the brain and microglial activation, besides controlling parasitemia and antigen-specific T-cell activation. Among different TLR-deficient mice studied, TLR9 mediated parasitemia control and T-cell penetration into the brain. TLR-MyD88 signals increased levels of interferon (IFN) β and tumor necrosis factor (TNF) α transcripts in the brains of infected mice and both TNF-α and IFN-α/β, receptors promoted T-cell and trypanosoma infiltration into the brain parenchyma. Both resident and infiltrating inflammatory cells in the brain controlled parasite densities in a TLR2- and TLR9-MyD88-mediated manner. However, neither IFN-α/β nor TNF-α contributed to parasite control in the brain.

Conclusions: Our data indicate that innate immune TLR signals stimulate the expression of TNF-α and IFN-α/β that initiate brain invasion of T cells and trypanosomes, and control T. brucei brucei load in the brain by molecules distinct from these.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / immunology
  • Blood-Brain Barrier / parasitology
  • Brain / immunology*
  • Brain / parasitology
  • Brain / pathology
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Immunity, Innate
  • Interferon-beta / metabolism
  • Interferon-gamma / blood
  • Interferon-gamma / immunology
  • Mice
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / deficiency
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / metabolism*
  • Parasite Load
  • Parasitemia / immunology
  • RNA, Messenger / metabolism*
  • Receptor, Interferon alpha-beta / immunology
  • Signal Transduction
  • Toll-Like Receptor 2 / metabolism
  • Toll-Like Receptor 9 / metabolism
  • Trypanosoma brucei brucei*
  • Trypanosomiasis, African / immunology*
  • Trypanosomiasis, African / metabolism
  • Trypanosomiasis, African / parasitology
  • Tumor Necrosis Factor-alpha / metabolism


  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • RNA, Messenger
  • Toll-Like Receptor 2
  • Toll-Like Receptor 9
  • Tumor Necrosis Factor-alpha
  • Receptor, Interferon alpha-beta
  • Interferon-beta
  • Interferon-gamma