Abstract
This study develops an original co-infection model in mice using Brucella melitensis, the most frequent cause of human brucellosis, and Trypanosoma brucei, the agent of African trypanosomiasis. Although the immunosuppressive effects of T. brucei in natural hosts and mice models are well established, we observed that the injection of T. brucei in mice chronically infected with B. melitensis induces a drastic reduction in the number of B. melitensis in the spleen, the main reservoir of the infection. Similar results are obtained with Brucella abortus- and Brucella suis-infected mice and B. melitensis-infected mice co-infected with Trypanosoma cruzi, demonstrating that this phenomenon is not due to antigenic cross-reactivity. Comparison of co-infected wild-type and genetically deficient mice showed that Brucella 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 T. brucei on B. melitensis were similar, suggesting that a chronic intense inflammatory reaction is not required to eliminate B. melitensis. Finally, we also tested the impact of T. brucei infection on the course of Mycobacterium tuberculosis infection. Although T. brucei strongly increases the frequency of IFNγ+CD4+ T cells, it does not ameliorate the control of M. tuberculosis infection, suggesting that it is not controlled by the same effector mechanisms as Brucella. Thus, whereas T. brucei infections are commonly viewed as immunosuppressive and pathogenic, our data suggest that these parasites can specifically affect the immune control of Brucella infection, with benefits for the host.
Highlights
In natural populations, individual resistance to infection is remarkably diverse
B. melitensis Persists in CD11c+ Reservoir Cells in the Spleen and Is Able to Resist to Protective Memory Immune Response
Following i.n. administration of 2 × 104 CFU of B. melitensis, we have shown previously [16] that the bacteria persist in the lungs up to 12 days postinfection and the spleen and liver are colonized starting 5 days postinfection
Summary
Individual resistance to infection is remarkably diverse. This has been linked to many factors [reviewed in Ref. Persistent infection can enhance the ability to control unrelated pathogens, a phenomenon termed the “Mackaness effect” in reference to the seminal work of Mackaness [2, 3] demonstrating cross-protection between L. monocytogenes, T. brucei Infection Increases Brucella Control. Since this pioneering work, numerous examples of the Mackaness effect have been reported. Herpes virus infection can provide beneficial protection against L. monocytogenes and Yersinia pestis [4]. As multiple unrelated infections in the same host are probably more common than single infections, it would be interesting to better understand the mechanisms underlying these crossprotections or cross-aggravations
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
