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

Abstract

The specific immune response against pathogenic microorganisms develops mainly in secondary lymphoid organs (SLOs) such as the spleen and lymph nodes. The architecture of SLOs finely tunes the immune response by regulating the interactions between different cells of the innate and adaptive immunity. The spleen is a sophisticated filter that manages blood cells and monitors immune functions. Micro-anatomically, the spleen is divided into white pulp and red pulp separated by the marginal zone (MZ). The MZ forms the outer boundary of the white pulp in the mouse spleen. The MZ plays a critical role in defense against pathogens that have entered the circulation. Two distinct macrophages populations are present in the MZ namely: marginal zone macrophages (MZM) and marginal metallophilic macrophages (MMM) that are localized at the outer and inner border of the MZ, respectively. Within the white pulp, T and B lymphocytes are also segregated into discrete compartments; B cells are situated in follicles, while T cells are located in an area around the central arteriole. It has been reported that viral and parasitic infections induced significant remodeling of splenic microarchitecture, including loss of marginal zone macrophages population and disappearance of T and B cells compartmentalization. The impact of bacterial infection on splenic microarchitecture has been poorly investigated.

In this work, we analyzed the impact of infection with B. melitensis on the structure and the cellular composition of the spleen by flow cytometry techniques and immunohistofluorescence in a mouse model. Brucella is facultative intracellular bacteria that chronically infect humans and animals causing brucellosis, a worldwide zoonosis. The protection against B. melitensis infections in mice model mainly requires CD4+ T lymphocytes, Th1-type cytokines such as interferon (IFN)-γ that mediated activation of microbicide functions of macrophages and inflammatory dendritic cells. We observed that B. melitensis causes alteration of the marginal zone and relocation of T cells to the red pulp. This reorganization is associated with a massive increase in absolute numbers of macrophages, neutrophils and dendritic cells and a slight decrease in lymphocytes. These alterations are partially dependent on interleukin-12. These observations raise the question of the influence of chronic infection with B. melitensis on the ability of the immune system to develop an immune response during vaccination or control a new infection.

Date of Award	28 Apr 2016
Original language	English
Awarding Institution	University of Namur
Supervisor	JEAN-JACQUES LETESSON (Supervisor), Eric Muraille (Co-Supervisor), Xavier De Bolle (President), Carlos GRAUX (Jury), Ayman Almariri (Jury), David Fretin (Jury) & Yves Poumay (Jury)