Differential Invasion of Trypanosoma brucei brucei and Lymphocytes into the Brain of C57BL/6 and 129Sv/Ev Mice

Abstract

Trypanosoma brucei subspecies invade the brain parenchyma at late stages of human and experimental rodent infections. In this study, we compared the outcome of infection with T. b. brucei in MHC‐matched (H‐2b) C57BL/6 (B6) and 129Sv/Ev (Sv‐129). Sv‐129 showed higher parasitaemia and lower specific IgM (but not IgG) antibody levels than B6 mice. The number of trypanosomes, CD4+ and CD8+ T cells in the brain parenchyma was higher in B6 mice. B6 mice lost weight and showed higher cumulative mortality when compared with Sv‐129 mice. Higher levels of IL‐1β, IL‐6, IL‐10, TNF‐α, IFN‐γ, ICAM‐1 and E‐selectin, but low levels of TGF‐β mRNA were present in brains of B6 when compared with Sv‐129‐infected mice. Thus, host genetics differentially determine the invasion of T. b. brucei into the brain parenchyma, which is paralleled by the severity of inflammation in the brain and course of the disease, but not by parasitaemia nor by antibody titres.

Trypanosoma brucei Invasion and T-Cell Infiltration of the Brain Parenchyma in Experimental Sleeping Sickness: Timing and Correlation with Functional Changes

“…Cyclical appearance of the parasites has also been observed in the CSF, with about one day delay with respect to parasitaemia, after intrathecal infection, in a paradigm in which parasite crossing of the blood-CSF barrier in the choroid plexus has been hypothesised [42]. There is mounting evidence to suggest that the neuroinflammatory response is the key parameter for parasite neuroinvasion, as a dissociation between parasitaemia and severity of brain inflammation has been reported in murine models of the infection [45]. …”

Alterations of orexinergic and melanin-concentrating hormone neurons in experimental sleeping sickness

“…In our infection paradigm T. b. brucei-infected rats survive 35-45 days, T. b. bruceiinfected mice survive about 35 days, and parasite invasion of the CNS starts in both species during the second week of disease, around dpi 11-12 (Masocha et al, 2004(Masocha et al, , 2008.…”

“…Murine models are widely adopted in experimental investigations on sleeping sickness (Antoine-Moussiaux et al, 2008;Masocha et al, 2008;Kristensson et al, 2010), and OX-A and MCH neurons were also investigated in mice at an advanced stage of disease (dpi 30). The mice were sacrificed during daytime and nighttime, at ZT4 and ZT16 (cage mates were sacrificed at 5-min intervals), and baseline expression of c-Fos was investigated in these animals left undisturbed in their home cages.…”

Protein kinase Cθ: the pleiotropic T-cell signalling intermediate

“…A systematic comparison of the phenotypic features of these PKCθ-knockout lines is given in Table 1. Additionally, the different genetic background of animals, namely C57B/6 in the previous [30][31][32] and 129/Sv in the recent [33] research work, might explain the divergent outcomes of Th17 experiments [34]. A pivotal importance of genetic environment for manifestation of PKCθ-knockout phenotype has also been observed previously in experiments with C57B/6 compared with BALBc mice [17].…”