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

(2012) PLOS PATHOGENS. 8(3).
Author
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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-gamma 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.
Keywords
DENDRITIC CELLS, ABORTUS INFECTION, MYCOBACTERIUM-TUBERCULOSIS, INTERFERON-GAMMA, MYD88-DEFICIENT MICE, FLUORESCENT PROTEIN, FOAMY MACROPHAGES, VIRB MUTANT, BALB/C MICE, MELITENSIS

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Chicago
Copin, Richard, Marie-Alice Vitry, Delphine Hanot Mambres, Arnaud Machelart, Carl De Trez, Jean-Marie Vanderwinden, Stefan Magez, et al. 2012. “In Situ Microscopy Analysis Reveals Local Innate Immune Response Developed Around Brucella Infected Cells in Resistant and Susceptible Mice.” Plos Pathogens 8 (3).
APA
Copin, R., Vitry, M.-A., Mambres, D. H., Machelart, A., De Trez, C., Vanderwinden, J.-M., Magez, S., et al. (2012). In situ microscopy analysis reveals local innate immune response developed around Brucella infected cells in resistant and susceptible mice. PLOS PATHOGENS, 8(3).
Vancouver
1.
Copin R, Vitry M-A, Mambres DH, Machelart A, De Trez C, Vanderwinden J-M, et al. In situ microscopy analysis reveals local innate immune response developed around Brucella infected cells in resistant and susceptible mice. PLOS PATHOGENS. 2012;8(3).
MLA
Copin, Richard et al. “In Situ Microscopy Analysis Reveals Local Innate Immune Response Developed Around Brucella Infected Cells in Resistant and Susceptible Mice.” PLOS PATHOGENS 8.3 (2012): n. pag. Print.
@article{8131771,
  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-gamma 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.},
  articleno    = {e1002575},
  author       = {Copin, Richard and Vitry, Marie-Alice and Mambres, Delphine Hanot and Machelart, Arnaud and De Trez, Carl and Vanderwinden, Jean-Marie and Magez, Stefan and Akira, Shizuo and Ryffel, Bernhard and Carlier, Yves and Letesson, Jean-Jacques and Muraille, Eric},
  issn         = {1553-7366},
  journal      = {PLOS PATHOGENS},
  language     = {eng},
  number       = {3},
  pages        = {18},
  title        = {In situ microscopy analysis reveals local innate immune response developed around Brucella infected cells in resistant and susceptible mice},
  url          = {http://dx.doi.org/10.1371/journal.ppat.1002575},
  volume       = {8},
  year         = {2012},
}

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