Abstract
In a mouse model of pneumonia caused by Streptococcus pneumoniae, differences in the timing and vigor of the host inflammatory response have been associated with susceptibility to invasive disease. BALB/c and CBA/Ca mice are known to be resistant and susceptible to acute pneumococcal disease, respectively. In this study, we have demonstrated that BMM from BALB/c and CBA/Ca mice differ in their expression and regulation of TLR9 in response to S. pneumoniae. We have also shown that BMM from CBA/Ca mice failed to fully activate p38, NF-kappaB, and ERK 1/2 signaling pathways, resulting in reduced secretion of TNF-alpha and CCL5 in response to this pathogen. In addition, we have established that S. pneumoniae induced significant cell death in BMM from CBA/Ca mice. These findings indicate that variations between the two strains are likely to reflect differences in macrophage responses to the pathogen.
MeSH terms
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Acute Disease
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Animals
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Cell Death / immunology
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Chemokine CCL5 / immunology
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Chemokine CCL5 / metabolism
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Disease Models, Animal
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Inflammation / immunology
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Inflammation / metabolism
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MAP Kinase Signaling System / immunology*
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Macrophages / immunology*
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Macrophages / metabolism
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Male
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Mice
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Mice, Inbred BALB C
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Mitogen-Activated Protein Kinase 3 / immunology
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Mitogen-Activated Protein Kinase 3 / metabolism
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NF-kappa B / immunology
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NF-kappa B / metabolism
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Pneumonia, Pneumococcal / immunology*
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Pneumonia, Pneumococcal / metabolism
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Species Specificity
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Streptococcus pneumoniae / immunology*
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Streptococcus pneumoniae / metabolism
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Toll-Like Receptor 9 / biosynthesis
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Toll-Like Receptor 9 / immunology
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Tumor Necrosis Factor-alpha / immunology
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Tumor Necrosis Factor-alpha / metabolism
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p38 Mitogen-Activated Protein Kinases / immunology
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Ccl5 protein, mouse
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Chemokine CCL5
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NF-kappa B
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Tlr9 protein, mouse
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Toll-Like Receptor 9
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Tumor Necrosis Factor-alpha
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Mitogen-Activated Protein Kinase 3
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p38 Mitogen-Activated Protein Kinases