title: Identification of Immune Effectors Essential to the Control of Primary and Secondary Intranasal Infection with Brucella melitensis in Mice.
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.
authors.affiliation: Microorganisms Biology Research Unit (URBM), Laboratory of Immunology and Microbiology, Namur Research Institute for Life Sciences, University of Namur, 5000 Namur, Belgium;
authors.forename: Delphine
authors.initials: D
authors.lastname: Hanot Mambres
authors.affiliation: Microorganisms Biology Research Unit (URBM), Laboratory of Immunology and Microbiology, Namur Research Institute for Life Sciences, University of Namur, 5000 Namur, Belgium;
authors.forename: Arnaud
authors.initials: A
authors.lastname: Machelart
authors.affiliation: Microorganisms Biology Research Unit (URBM), Laboratory of Immunology and Microbiology, Namur Research Institute for Life Sciences, University of Namur, 5000 Namur, Belgium;
authors.forename: Georges
authors.identifier: 0000-0002-4226-1845
authors.initials: G
authors.lastname: Potemberg
authors.affiliation: Department of Molecular and Cellular Interactions, Flanders Interuniversity Institute for Biotechnology, Free University of Brussels (VUB), 1050 Brussels, Belgium;
authors.forename: Carl
authors.initials: C
authors.lastname: De Trez
authors.affiliation: Immunologie et Neurogénétique Expérimentales et Moléculaires - UMR7355 CNRS - Université d'Orléans, 45071 Orleans, France; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Capetown 7925, South Africa; and.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.affiliation: Microorganisms Biology Research Unit (URBM), Laboratory of Immunology and Microbiology, Namur Research Institute for Life Sciences, University of Namur, 5000 Namur, Belgium;
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Letesson
authors.affiliation: Microorganisms Biology Research Unit (URBM), Laboratory of Immunology and Microbiology, Namur Research Institute for Life Sciences, University of Namur, 5000 Namur, Belgium; Laboratoire de Parasitologie, Faculté de Médecine, Université Libre de Bruxelles, 1070 Bruxelles, Belgium emuraille@hotmail.com.
authors.forename: Eric
authors.initials: E
authors.lastname: Muraille
mesh_terms: D000818:Animals; D017347:Brucella melitensis / Q000276:immunology*; D002006:Brucellosis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D018928:Immunity, Mucosal; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010256:Paranasal Sinuses / Q000382:microbiology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000378:metabolism; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C491673:Il17ra protein, mouse; D016692:Receptors, Antigen, T-Cell, gamma-delta; D053722:Receptors, Interleukin-17; D007371:Interferon-gamma