Different parasite inocula determine the modulation of the immune response and outcome of experimental Trypanosoma cruzi infection

Authors


Correspondence: Javier E. Lazo Chica, Institute of Biological and Natural Sciences, Federal University of Triângulo Mineiro, Praça Manoel Terra, 330 -38015-050, Uberaba, MG, Brazil. Email: jlazo@dcb.uftm.edu.br

Senior author: Javier Emilio Lazo Chica

Summary

During infection, the host response develops effector mechanisms to combat the parasite. However, this response can become uncontrolled or regulated by mechanisms that modulate the inflammatory reaction. The number of parasites that infects the host, such as trypomastigotes in Chagas disease, may also influence immune activation and disease pathology. We evaluated the inflammation and immune regulation that follows Trypanosoma cruzi infection with low (300), intermediate (3000) or high (30 000) parasite loads. Our results showed that the load of parasite inoculum influenced disease outcome: the higher the number of parasites in the inoculum, the lower were the survival rates. There was a strong association between parasitism and inflammatory infiltrate in the heart and the parasite inoculum determined cytokine interplay in this tissue, as shown by increased interferon-γ, tumour necrosis factor-α, interleukin-17 (IL-17) and IL-23 in the 300 and 30 000 inoculum groups, higher IL-4 and IL-10 in the intermediate-inoculum mice, and elevated IL-6 production in the heart of mice in the 3000 and 30 000 groups. The number of T cells and antigen-presenting cells was augmented in the infected groups, especially for the splenic CD4+ CD25+ regulatory T cells expressing CD45RBlow, GITR, PD-1 and FoxP3 in the group with the highest inoculum. Interestingly, these mice also presented an apparent decrease in CD4+ CD25+ FoxP3+ cells in the cardiac infiltrate, in contrast to the intermediate inoculum group, which showed elevated numbers of these regulatory leucocytes in the heart. Finally, our results demonstrated that parasite load during T. cruzi infection is linked to the response pattern that will result in parasite/inflammation control or tissue damage.

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