Mouse models for pathogenic African trypanosomes: unravelling the immunology of host–parasite–vector interactions

Abstract

African trypanosomiasis is a parasitic disease that affects a variety of mammals, including humans, on the sub-Saharan African continent. To understand the diverse parameters that govern the host-parasite-vector interactions, mouse models for the disease have proven to be a cornerstone. Despite the fact that most trypanosomes cannot be considered natural pathogens for rodents, experimental infections in mice have shed a tremendous amount of light on the general biology of these parasites and their interaction with and evasion of the mammalian immune system. Different aspects including inflammation, vaccine failure, antigenic variation, resistance/sensitivity to normal human serum and the influence of tsetse compounds on parasite transmission have all been addressed using mouse models. In more recent years, the introduction of various 'knock-out' mouse strains has allowed to analyse the implication of various cytokines, particularly TNF, IFNγ and IL-10, in the regulation of parasitaemia and induction of pathological conditions during infection.

Identification of Trans-Sialidases as a Common Mediator of Endothelial Cell Activation by African Trypanosomes

“…In such a model, parasites use different strategies to trigger anaemia and inflammation. This configuration is consistent with previous results showing that mice models respond differently to infections depending on the trypanosome species [54]. It also explains why in field infections, the severity of the disease and its physiopathological features are widely dependent on the trypanosome species and its specificities, such as the ability to invade tissues, the genetic variability between isolates (especially from distinct geographical regions) and above all the host range [55].…”

Comparative pathogenicity of Trypanosoma brucei rhodesiense strains in Swiss white mice and Mastomys natalensis rats

“…Further, it is important to note that parasitaemia levels were generally higher in mice compared to rats in the present study. Indeed, extremely high parasitaemia levels is one of the limitations of the mouse models of trypanosomiasis (Magez and Caljon, 2011). This agrees with earlier studies using EATRO 1989 and KETRI 3741 (Kibugu et al, 2009;Fink and Schmidt, 1979), the three trypanosome isolates used in the present study produced chronic infection in mice.…”

Translational Rodent Models for Research on Parasitic Protozoa—A Review of Confounders and Possibilities

“…In leishmaniasis research, rodents are acknowledged for contributing to a better understanding of the immune response to the parasite (Lipoldová and Demant, 2006) but other authors point out limitations and the lack of suitability of certain mouse strains to study specific parasite genotypes (Mears et al, 2015). Research on human sleeping sickness (T. brucei) has benefitted largely from mouse models (Antoine-Moussiaux et al, 2008;Giroud et al, 2009;Magez and Caljon, 2011) but criticism has been raised that more suitable animal models should be applied to address sleeping sickness in livestock (T. congolense and T. vivax; Morrison et al, 2016). (Figure 1A).…”