In Situ Characterization of Splenic Brucella melitensis Reservoir Cells during the Chronic Phase of Infection in Susceptible Mice

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

Research output: Contribution to journalArticle

109 Downloads (Pure)

Abstract

Brucella are facultative intracellular Gram-negative coccobacilli that chronically infect humans as well as domestic and wild-type mammals, and cause brucellosis. Alternatively activated macrophages (M2a) induced by IL-4/IL-13 via STAT6 signaling pathways have been frequently described as a favorable niche for long-term persistence of intracellular pathogens. Based on the observation that M2a-like macrophages are induced in the spleen during the chronic phase of B. abortus infection in mice and are strongly infected in vitro, it has been suggested that M2a macrophages could be a potential in vivo niche for Brucella. In order to test this hypothesis, we used a model in which infected cells can be observed directly in situ and where the differentiation of M2a macrophages is favored by the absence of an IL-12-dependent Th1 response. We performed an in situ analysis by fluorescent microscopy of the phenotype of B. melitensis infected spleen cells from intranasally infected IL-12p40-/- BALB/c mice and the impact of STAT6 deficiency on this phenotype. Most of the infected spleen cells contained high levels of lipids and expressed CD11c and CD205 dendritic cell markers and Arginase1, but were negative for the M2a markers Fizz1 or CD301. Furthermore, STAT6 deficiency had no effect on bacterial growth or the reservoir cell phenotype in vivo, leading us to conclude that, in our model, the infected cells were not Th2-induced M2a macrophages. This characterization of B. melitensis reservoir cells could provide a better understanding of Brucella persistence in the host and lead to the design of more efficient therapeutic strategies.

Original languageEnglish
Pages (from-to)e0137835
JournalPLoS ONE
Volume10
Issue number9
DOIs
Publication statusPublished - 2015

Fingerprint Dive into the research topics of 'In Situ Characterization of Splenic Brucella melitensis Reservoir Cells during the Chronic Phase of Infection in Susceptible Mice'. Together they form a unique fingerprint.

  • Projects

    Equipment

  • Morphology - Imaging

    Charles Nicaise (Manager) & Francesca Cecchet (Manager)

    Technological Platform Morphology - Imaging

    Facility/equipment: Technological Platform

  • Student Theses

    Characterization of the relationship between Brucella melitensis and the innate immune system of the mouse

    Author: Copin, R., 28 Sep 2010

    Supervisor: Letesson, J. (Supervisor), Moriyón, I. (External person) (Jury), Magez, S. (External person) (Jury), LOCHT, C. (External person) (Jury) & Muraille, É. (Co-Supervisor)

    Student thesis: Doc typesDoctor of Sciences

    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

    File

    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

    File

    Cite this