Identification of Immune Effectors Essential to the Control of Primary and Secondary Intranasal Infection with Brucella melitensis in Mice

Delphine Hanot Mambres, Arnaud Machelart, Georges Potemberg, Carl De Trez, Bernhard Ryffel, Jean-Jacques Letesson, Eric Muraille

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Abstract

The mucosal immune system represents the first line of defense against Brucella infection in nature. We used genetically deficient mice to identify the lymphocytes and signaling pathways implicated in the control of primary and secondary intranasal infection with B. melitensis Our analysis of primary infection demonstrated that the effectors implicated differ at the early and late stages and are dependent on the organ. TCR-δ, TAP1, and IL-17RA deficiency specifically affects early control of Brucella in the lungs, whereas MHC class II (MHCII) and IFN-γR deficiency impairs late control in the lungs, spleen, and liver. Interestingly, IL-12p35(-/-) mice display enhanced Brucella growth in the spleen but not in the lungs or liver. Secondary intranasal infections are efficiently contained in the lung. In contrast to an i.p. infectious model, in which IL-12p35, MHCII, and B cells are strictly required for the control of secondary infection, we observed that only TCR-β deficiency or simultaneous neutralization of IL-12p35- and IL-17A-dependent pathways impairs the memory protective response against a secondary intranasal infection. Protection is not affected by TCR-δ, MHCII, TAP1, B cell, IL-17RA, or IL-12p35 deficiency, suggesting that CD4(+) and CD8(+) α/β(+) T cells are sufficient to mount a protective immune response and that an IL-17A-mediated response can compensate for the partial deficiency of an IFN-γ-mediated response to control a Brucella challenge. These findings demonstrate that the nature of the protective memory response depends closely on the route of infection and highlights the role of IFN-γ-and IL-17RA-mediated responses in the control of mucosal infection by Brucella.

Original languageEnglish
Pages (from-to)3780-93
Number of pages14
JournalJournal of immunology
Volume196
Issue number9
DOIs
Publication statusPublished - 2016

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    Impact de l'asthme allergique et de l'infection par Trypanosoma brucei sur le contrôle de l’infection par Brucella melitensis chez la souris

    Author: MacHelart, A., 2 Dec 2016

    Supervisor: Letesson, J. (Supervisor), Muraille, É. (Co-Supervisor), Cornelis, G. (President), Coutelier, J. (External person) (Jury), Gillet, L. (External person) (Jury) & Godfroid, J. (External person) (Jury)

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    Relationship between Brucella melitensis and the associated immune response after intranasal infection in mice

    Author: Hanot-Mambres, D., 4 Dec 2014

    Supervisor: Letesson, J. (Supervisor), Muylkens, B. (Jury), Huygen, K. (External person) (Jury), LOCHT, C. (External person) (Jury), Godfroid, J. (External person) (Jury) & MURAILLE, E. (External person) (Supervisor)

    Student thesis: Doc typesDoctor of Sciences

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