In Situ Microscopy Analysis Reveals Local Innate Immune Response Developed around Brucella Infected Cells in Resistant and Susceptible Mice

PLoS Pathogens

Shizuo Akira¹  Carl De Trez²  Stefan Magez²  Jean-Marie Vanderwinden³  Yves Carlier⁴  Eric Muraille⁴  Marie-Alice Vitry⁵  Delphine Hanot Mambres⁵  Arnaud Machelart⁵  Richard Copin⁵  Jean-Jacques Letesson⁵  Bernhard Ryffel⁶ 

[1] Department of Host Defense, Research Institute for Microbial Diseases, Osaka University Yamadaoka, Suita City, Osaka, Japan;Department of Molecular and Cellular Interactions, Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Brussels, Belgium;Laboratoire de Neurophysiologie, Faculté de Médecine, Université Libre de Bruxelles, Bruxelles, Belgium;Laboratoire de Parasitologie, Faculté de Médecine, Université Libre de Bruxelles, Bruxelles, Belgium;Unité de Recherche en Biologie Moléculaire, Laboratoire d'Immunologie et de Microbiologie, Faculté Universitaire Notre Dame de la Paix, Namur, Belgium;University of Orleans, Transgenose Institute, Laboratoire d'Immunologie et d'Embryologie Moléculaires, CNRS, UMR 6218, Orleans, France

关键词: Spleen;    Brucella;    Granulomas;    Macrophages;    T cells;    Immune response;    Mouse models;    Flow cytometry;   

DOI  :  10.1371/journal.ppat.1002575

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Brucella are facultative intracellular bacteria that chronically infect humans and animals causing brucellosis. Brucella are able to invade and replicate in a broad range of cell lines in vitro, however the cells supporting bacterial growth in vivo are largely unknown. In order to identify these, we used a Brucella melitensis strain stably expressing mCherry fluorescent protein to determine the phenotype of infected cells in spleen and liver, two major sites of B. melitensis growth in mice. In both tissues, the majority of primary infected cells expressed the F4/80 myeloid marker. The peak of infection correlated with granuloma development. These structures were mainly composed of CD11b+ F4/80+ MHC-II+ cells expressing iNOS/NOS2 enzyme. A fraction of these cells also expressed CD11c marker and appeared similar to inflammatory dendritic cells (DCs). Analysis of genetically deficient mice revealed that differentiation of iNOS+ inflammatory DC, granuloma formation and control of bacterial growth were deeply affected by the absence of MyD88, IL-12p35 and IFN-γ molecules. During chronic phase of infection in susceptible mice, we identified a particular subset of DC expressing both CD11c and CD205, serving as a reservoir for the bacteria. Taken together, our results describe the cellular nature of immune effectors involved during Brucella infection and reveal a previously unappreciated role for DC subsets, both as effectors and reservoir cells, in the pathogenesis of brucellosis.

【 授权许可】

CC BY