title: 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.
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.
authors: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors: Daniel Ndem
authors: DN
authors: Amin
authors: Suman K
authors: SK
authors: Vodnala
authors: Willias
authors: W
authors: Masocha
authors: Bo
authors: B
authors: Sun
authors: Krister
authors: K
authors: Kristensson
authors: Martin E
authors: ME
authors: Rottenberg
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology / Q000469:parasitology; D001921:Brain / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D007113:Immunity, Innate; D016899:Interferon-beta / Q000378:metabolism; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D059208:Parasite Load; D018512:Parasitemia / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism*; D053633:Receptor, Interferon alpha-beta / Q000276:immunology; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D014346:Trypanosoma brucei brucei; D014353:Trypanosomiasis, African / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta; D007371:Interferon-gamma