A mathematical model of Chagas disease infection predicts inhibition of the immune system

The protozoan parasite Trypanosoma cruz causes the Chagas disease, which final outcome can be morbidity or death. The complexity of this infection is due to the many kinds of players involved in the immune response and to the variety of host cells targeted by the parasite. We built an ordinary differential equation model which includes aspects of innate and adaptive immune response to study the T. cruzi infection. The model also includes cardiomyocytes to represent how the infection affects the heart. We used parasitemia experimental data of infected wild-type mice to estimate the model parameters. We investigated how the number of parasites and infected cardiomyocytes were affected by changes of parameters controlling the survival rates of the parasite. We thus introduce a 20% variation in either macrophages, CDS+T cells, or anti- parasite specific antibody activity. This resulted in a change of the parasitemia as expected, and produced a broader variation in the number of parasites around the peak of parasitemia. Moreover, the same three model modifications were enabled one at a time to simulate a knockout effect in the host. The results of the knockout effects were a faster parasite growth and death of the host in all three cases, in agreement with in vivo experimental data. The model also is corroborated by in vivo data from the literature where the inhibition of macrophages, antibody, or CTL is not compensated by the other parasite killing mechanisms, and as a result lead to death of the host. Altogether these results indicate that the immune system plays a crucial role in controlling T. cruzi infection and impairment of one modality of action greatly reduces its efficiency and results in a much larger extensionof the infection of cardiomyocytes.