Abstract
Francisella tularensis causes pulmonary tularemia and death in humans when left untreated. Here, using a novel aerosol infection model, we show that acute pulmonary Francisella novicida infection not only causes pneumonia and liver damage, but also induces dystrophic cardiac calcinosis (DCC) in BALB/c mice. C57BL/6 mice also develop pneumonia and hepatic damage, but fail to develop DCC. Development of DCC in BALB/c mice is associated with significant induction of RANKL but not osteopontin in their organs. Depletion of lung macrophages prior to infection markedly reduces pericarditis and calcification in BALB/c mice but does not increase their susceptibility to infection.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calcinosis / metabolism
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Calcinosis / microbiology*
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Cardiomyopathies / metabolism
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Cardiomyopathies / microbiology*
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Female
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Francisella / growth & development*
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Gram-Negative Bacterial Infections / metabolism*
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Gram-Negative Bacterial Infections / microbiology
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Interleukin-1 / biosynthesis
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Interleukin-1 / genetics
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Interleukin-6 / biosynthesis
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Interleukin-6 / genetics
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Liver / metabolism
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Liver / microbiology
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Lung / metabolism
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Lung / microbiology
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Macrophages / metabolism
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Macrophages / microbiology
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Osteopontin / biosynthesis
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Osteopontin / genetics
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RANK Ligand / biosynthesis
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RANK Ligand / genetics
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Respiratory Tract Infections / metabolism*
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Respiratory Tract Infections / microbiology
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Reverse Transcriptase Polymerase Chain Reaction
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Specific Pathogen-Free Organisms
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / immunology
Substances
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Interleukin-1
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Interleukin-6
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RANK Ligand
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RNA, Messenger
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Spp1 protein, mouse
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Tnfsf11 protein, mouse
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Tumor Necrosis Factor-alpha
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Osteopontin