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

Machelart, Arnaud; Vyve, Margaux Van; Potemberg, Georges; Demars, Aurore; Trez, Carl De; Tima, Hermann Giresse; Vanwalleghem, Gilles; Romano, Márta; Truyens, Carine; Letesson, Jean‐Jacques; Muraille, Eric

doi:10.3389/fimmu.2017.00903

Cited by 11 publications

(15 citation statements)

References 49 publications

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“…This may be the consequence of the higher number of CD4 + T cells in absence of CD8 + T cell in TAP1 −/− mice. In a previous study (47), we demonstrated that even though the amounts of IFN-γ produced by CD8 + T cells and CD4 + T cells are similar, CD8 + T cells are unable to replace CD4 + T cells in their control of Brucella infection, suggesting that CD4 + T cells deploy as yet unidentified effector mechanisms that may be independent of IFN-γ. In the i.d.…”

Section: Resultsmentioning

confidence: 74%

Route of Infection Strongly Impacts the Host-Pathogen Relationship

et al. 2019

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Live attenuated vaccines play a key role in the control of many human and animal pathogens. Their rational development is usually helped by identification of the reservoir of infection, the lymphoid subpopulations associated with protective immunity as well as the virulence genes involved in pathogen persistence. Here, we compared the course of Brucella melitensis infection in C57BL/6 mice infected via intraperitoneal (i.p.), intranasal (i.n.) and intradermal (i.d.) route and demonstrated that the route of infection strongly impacts all of these parameters. Following i.p. and i.n. infection, most infected cells observed in the spleen or lung were F4/80 + myeloid cells. In striking contrast, infected Ly6G + neutrophils and CD140a + fibroblasts were also observed in the skin after i.d. infection. The virB operon encoding for the type IV secretion system is considered essential to deflecting vacuolar trafficking in phagocytic cells and allows Brucella to multiply and persist. Unexpectedly, the Δ virB Brucella strain, which does not persist in the lung after i.n. infection, persists longer in skin tissues than the wild strain after i.d. infection. While the CD4 + T cell-mediated Th1 response is indispensable to controlling the Brucella challenge in the i.p. model, it is dispensable for the control of Brucella in the i.d. and i.n. models. Similarly, B cells are indispensable in the i.p. and i.d. models but dispensable in the i.n. model. γδ + T cells appear able to compensate for the absence of αβ + T cells in the i.d. model but not in the other models. Taken together, our results demonstrate the crucial importance of the route of infection for the host pathogen relationship.

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Section: Resultsmentioning

confidence: 74%

Route of Infection Strongly Impacts the Host-Pathogen Relationship

et al. 2019

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“…This suggests that the strong pro-inflammatory IFNγ-mediated immune response induced by the T. brucei infection aided the clearance of Brucella . Thus, although infections with T. brucei can induce significant levels of immunosuppression and immunopathology, this study shows that under some circumstances the host's response to T. brucei infection may provide protection against co-infection with other pathogens ( 41 ). However, this not true for all pathogenic bacteria.…”

Section: Trypanosomesmentioning

confidence: 85%

“…Trypanosome infections may also modulate host susceptibility to infection with some pathogenic bacteria. For example, in mice chronically-infected with either Brucella melitensis, B. abortus , or B. suis , the burden of bacteria in the spleen was reduced if the mice were also co-infected with T. brucei ( 41 ). The effects of T. brucei infection on Brucella burdens in co-infected mice were impeded in the absence of functional IL-12p35/IFNγ signaling.…”

Section: Trypanosomesmentioning

confidence: 99%

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The Influence of Parasite Infections on Host Immunity to Co-infection With Other Pathogens

Mabbott

2018

Front. Immunol.

110

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Parasites have evolved a wide range of mechanisms that they use to evade or manipulate the host's immune response and establish infection. The majority of the in vivo studies that have investigated these host-parasite interactions have been undertaken in experimental animals, especially rodents, which were housed and maintained to a high microbiological status. However, in the field situation it is increasingly apparent that pathogen co-infections within the same host are a common occurrence. For example, chronic infection with pathogens including malarial parasites, soil-transmitted helminths, Mycobacterium tuberculosis and viruses such as HIV may affect a third of the human population of some developing countries. Increasing evidence shows that co-infection with these pathogens may alter susceptibility to other important pathogens, and/or influence vaccine efficacy through their effects on host immune responsiveness. Co-infection with certain pathogens may also hinder accurate disease diagnosis. This review summarizes our current understanding of how the host's immune response to infection with different types of parasites can influence susceptibility to infection with other pathogenic microorganisms. A greater understanding of how infectious disease susceptibility and pathogenesis can be influenced by parasite co-infections will enhance disease diagnosis and the design of novel vaccines or therapeutics to more effectively control the spread of infectious diseases.

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“…We observed recently ( 87 ) that the strong Th1 response induced by Trypanosoma brucei infection significantly reduced Brucella growth but did not affect the course of M. tuberculosis infection in mice. Taken together, the absence of an impact of the Th1 response induced by T. brucei and the Th2 response induced by asthmatic sensitization on M. tuberculosis infection in our mice models is very surprising and suggests that control of M. tuberculosis is not simply dependent on a balance between the Th1 and Th2 responses.…”

Section: Discussionmentioning

confidence: 90%

Allergic Asthma Favors Brucella Growth in the Lungs of Infected Mice

et al. 2018

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Allergic asthma is a chronic Th2 inflammatory disease of the lower airways affecting a growing number of people worldwide. The impact of infections and microbiota composition on allergic asthma has been investigated frequently. Until now, however, there have been few attempts to investigate the impact of asthma on the control of infectious microorganisms and the underlying mechanisms. In this work, we characterize the consequences of allergic asthma on intranasal (i.n.) infection by Brucella bacteria in mice. We observed that i.n. sensitization with extracts of the house dust mite Dermatophagoides farinae or the mold Alternaria alternata (Alt) significantly increased the number of Brucella melitensis, Brucella suis, and Brucella abortus in the lungs of infected mice. Microscopic analysis showed dense aggregates of infected cells composed mainly of alveolar macrophages (CD11c+ F4/80+ MHCII+) surrounded by neutrophils (Ly-6G+). Asthma-induced Brucella susceptibility appears to be dependent on CD4+ T cells, the IL-4/STAT6 signaling pathway and IL-10, and is maintained in IL-12- and IFN-γR-deficient mice. The effects of the Alt sensitization protocol were also tested on Streptococcus pneumoniae and Mycobacterium tuberculosis pulmonary infections. Surprisingly, we observed that Alt sensitization strongly increases the survival of S. pneumoniae infected mice by a T cell and STAT6 independent signaling pathway. In contrast, the course of M. tuberculosis infection is not affected in the lungs of sensitized mice. Our work demonstrates that the impact of the same allergic sensitization protocol can be neutral, negative, or positive with regard to the resistance of mice to bacterial infection, depending on the bacterial species.

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

Cited by 11 publications

References 49 publications

Route of Infection Strongly Impacts the Host-Pathogen Relationship

Route of Infection Strongly Impacts the Host-Pathogen Relationship

The Influence of Parasite Infections on Host Immunity to Co-infection With Other Pathogens

Allergic Asthma Favors Brucella Growth in the Lungs of Infected Mice

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