Trypanosoma Infection Favors Brucella Elimination via IL-12/IFNγ-Dependent Pathways

Abstract

This study develops an original co-infection model in mice using <i>Brucella melitensis</i>, the most frequent cause of human brucellosis, and <i>Trypanosoma brucei</i>, the agent of African trypanosomiasis. Although the immunosuppressive effects of <i>T. brucei</i> in natural hosts and mice models are well established, we observed that the injection of <i>T. brucei</i> in mice chronically infected with <i>B. melitensis</i> induces a drastic reduction in the number of <i>B. melitensis</i> in the spleen, the main reservoir of the infection. Similar results are obtained with <i>Brucella abortus</i>- and <i>Brucella suis</i>-infected mice and <i>B. melitensis</i>-infected mice co-infected with <i>Trypanosoma cruzi</i>, demonstrating that this phenomenon is not due to antigenic cross-reactivity. Comparison of co-infected wild-type and genetically deficient mice showed that <i>Brucella</i> elimination required functional IL-12p35/IFNγ signaling pathways and the presence of CD4⁺ T cells. However, the impact of wild type and an attenuated mutant of <i>T. brucei</i> on <i>B. melitensis</i> were similar, suggesting that a chronic intense inflammatory reaction is not required to eliminate <i>B. melitensis</i>. Finally, we also tested the impact of <i>T. brucei</i> infection on the course of <i>Mycobacterium tuberculosis</i> infection. Although <i>T. brucei</i> strongly increases the frequency of IFNγ⁺CD4⁺ T cells, it does not ameliorate the control of <i>M. tuberculosis</i> infection, suggesting that it is not controlled by the same effector mechanisms as <i>Brucella</i>. Thus, whereas <i>T. brucei</i> infections are commonly viewed as immunosuppressive and pathogenic, our data suggest that these parasites can specifically affect the immune control of <i>Brucella</i> infection, with benefits for the host.