The Journal of immunology (1950), 2016-03-01, Vol.196 (5), p.2239-2248
We used two different infection models to investigate the kinetics of the PcpA-dependent pneumococcal disease in mice. In a bacteremic pneumonia model, we observed a PcpA-dependent increase in bacterial burden in the lungs, blood, liver, bronchoalveolar lavage, and spleens of mice at 24 h postinfection. This PcpA-dependent effect on bacterial burden appeared earlier (within 12 h) in the focal pneumonia model, which lacks bacteremia or sepsis. Histological changes show that the ability of pneumococci to make PcpA was associated with unresolved inflammation in both models of infection. Using our bacteremic pneumonia model we further investigated the effects of PcpA on recruitment of innate immune regulatory cells. The presence of PcpA was associated with increased IL-6 levels, suppressed production of TRAIL, and reduced infiltration of polymorphonuclear cells. The ability of pneumococci to make PcpA negatively modulated both the infiltration and apoptosis of macrophages and the recruitment of myeloid-derived suppressor-like cells. The latter have been shown to facilitate the clearance and control of bacterial pneumonia. Taken together, the ability to make PcpA was strongly associated with increased bacterial burden, inflammation, and negative regulation of innate immune cell recruitment to the lung tissue during bacteremic pneumonia.
Streptococcus pneumoniae - immunology ; Time Factors ; Myeloid Cells - immunology ; Streptococcus pneumoniae - metabolism ; Inflammation Mediators - metabolism ; Streptococcus pneumoniae - genetics ; Female ; Bacterial Proteins - immunology ; Carrier Proteins - immunology ; Macrophages - immunology ; Disease Models, Animal ; Pneumonia, Pneumococcal - immunology ; Pneumonia, Pneumococcal - microbiology ; Macrophages - pathology ; Immunomodulation ; Bacterial Proteins - genetics ; Mice, Transgenic ; Bacterial Load ; Pneumonia, Pneumococcal - mortality ; TNF-Related Apoptosis-Inducing Ligand - metabolism ; Bacteremia ; Carrier Proteins - genetics ; Macrophages - metabolism ; Animals ; Carrier Proteins - metabolism ; Pneumonia, Pneumococcal - pathology ; Myeloid Cells - metabolism ; Bacterial Proteins - metabolism ; Mice ; Mutation ; Gene Expression Regulation, Bacterial ; Cytokines - biosynthesis ; Index Medicus ; Abridged Index Medicus
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