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

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.

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1
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Abstract

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.

PMID:
22116836
PMCID:
PMC3244369
DOI:
10.1093/infdis/jir734
[Indexed for MEDLINE]
Free PMC Article
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