Chronic Brucella Infection Induces Selective and Persistent Interferon Gamma-Dependent Alterations of Marginal Zone Macrophages in the Spleen

Arnaud Machelart, Abir Khadrawi, Aurore Demars, Kevin Willemart, Carl De Trez, Jean-Jacques Letesson, Eric Muraille

Research output: Contribution to journalArticle


The spleen is known as an important filter for blood-borne pathogens that are trapped by specialized macrophages in the marginal zone (MZ): the CD209+MZ macrophages (MZMs) and the CD169+marginal metallophilic macrophages (MMMs). Acute systemic infection strongly impacts MZ populations and the location of T and B lymphocytes. This phenomenon has been linked to reduced chemokine secretion by stromal cells.Brucellaspp. are the causative agent of brucellosis, a widespread zoonotic disease. Here, we usedBrucella melitensisinfection as a model to investigate the impact of chronic stealth infection on splenic MZ macrophage populations. During the late phase ofBrucellainfection, we observed a loss of both MZMs and MMMs, with a durable disappearance of MZMs, leading to a reduction of the ability of the spleen to take up soluble antigens, beads, and unrelated bacteria. This effect appears to be selective as every other lymphoid and myeloid population analyzed increased during infection, which was also observed followingBrucella abortusandBrucella suisinfection. Comparison of wild-type and deficient mice suggested that MZ macrophage population loss is dependent on interferon gamma (IFN-γ) receptor but independent of T cells or tumor necrosis factor alpha receptor 1 (TNF-αR1) signaling pathways and is not correlated to an alteration of CCL19, CCL21, and CXCL13 chemokine mRNA expression. Our results suggest that MZ macrophage populations are particularly sensitive to persistent low-level IFN-γ-mediated inflammation and thatBrucellainfection could reduce the ability of the spleen to perform certain MZM- and MMM-dependent tasks, such as antigen delivery to lymphocytes and control of systemic infection.

Original languageEnglish
Article numbere00115-17
JournalInfection and Immunity
Issue number11
Publication statusPublished - Nov 2017
Externally publishedYes


  • Animals
  • Anti-Bacterial Agents/pharmacology
  • B-Lymphocytes/immunology
  • Brucella abortus/drug effects
  • Brucella melitensis/drug effects
  • Brucella suis/drug effects
  • Brucellosis/drug therapy
  • Chemokine CCL19/genetics
  • Chemokine CCL21/genetics
  • Chemokine CXCL13/genetics
  • Chronic Disease
  • Gene Expression Regulation
  • Host-Pathogen Interactions
  • Interferon-gamma/genetics
  • Macrophages/immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • RNA, Messenger/genetics
  • Receptors, Interferon/deficiency
  • Receptors, Tumor Necrosis Factor, Type I/deficiency
  • Rifampin/pharmacology
  • Signal Transduction
  • Spleen/immunology
  • Streptomycin/pharmacology
  • T-Lymphocytes/immunology
  • Brucella melitensis
  • Spleen
  • Marginal zone macrophages
  • Infection
  • Brucellosis
  • Low-grade Th1 inflammation

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  • Student Theses

    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)

    Student thesis: Doc typesDoctor of Sciences


    Impact of Brucella melitensis infection on the splenic microarchitecture and splenic homeostasis in an experimental mouse model

    Author: Khadrawi, A., 28 Apr 2016

    Supervisor: Letesson, J. (Supervisor), MURAILLE, E. (External person) (Co-Supervisor), De Bolle, X. (President), GRAUX, C. (External person) (Jury), Almariri, A. (External person) (Jury), Fretin, D. (External person) (Jury) & Poumay, Y. (Jury)

    Student thesis: Doc typesDoctor of Sciences

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