In situ microscopy analysis reveals local innate immune response developed around Brucella infected cells in resistant and susceptible mice.

TitleIn situ microscopy analysis reveals local innate immune response developed around Brucella infected cells in resistant and susceptible mice.
Publication TypeJournal Article
Year of Publication2012
AuthorsCopin, R., Vitry M-A., Mambres D. Hanot, Machelart A., De Trez C., Vanderwinden J-M., Magez S., Akira S., Ryffel B., Carlier Y., Letesson J-J., and Muraille E.
JournalPLoS Pathog
Volume8
Issue3
Paginatione1002575
Date Published2012
Type of Articleimmunology
ISSN1553-7374
KeywordsAnimals, Biological Markers, Brucella, Brucellosis, Cell Separation, Dendritic Cells, Disease Models, Animal, Disease Susceptibility, Immunity, Innate, Liver, Lung Diseases, Mice, Mice, Inbred C57BL, Mice, Knockout, Nitric Oxide Synthase Type I, Nitric Oxide Synthase Type II, Phenotype, Spleen
Abstract

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.

DOI10.1371/journal.ppat.1002575
Alternate JournalPLoS Pathog.
PubMed ID22479178
PubMed Central IDPMC3315488