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Tumor necrosis factor-alpha deficiency impairs host defense against Streptococcus pneumoniae

Abstract

Streptococcus pneumoniae is a major human pathogen that is involved in community-acquired pneumonia. Tumor necrosis factor-alpha (TNF-α) is a pro-inflammatory cytokine that activates immune responses against infection, invasion, injury, or inflammation. To study the role of TNF-α during S. pneumoniae infection, a murine pneumococcal pneumonia model was used. We intranasally infected C57BL/6J wild-type (WT) and TNF-α knockout (KO) mice with S. pneumoniae D39 serotype 2. In TNF-α KO mice, continuous and distinct loss of body weight, and low survival rates were observed. Bacterial counts in the lungs and blood of TNF-α KO mice were significantly higher than those in WT mice. Histopathological lesions in the spleen of TNF-α KO mice were more severe than those in WT mice. In TNF-α KO mice, severe depletion of white pulp was observed and the number of apoptotic cells was significantly increased. Interferon-gamma (IFN-γ), IL-12p70 and IL-10 levels in serum were significantly increased in TNF-α KO mice. TNF-α is clearly involved in the regulation of S. pneumoniae infections. Early death and low survival rates of TNF-α KO mice were likely caused by a combination of impaired bacterial clearance and damage to the spleen. Our findings suggest that TNF-α plays a critical role in protecting the host from systemic S. pneumoniae infection.

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Acknowledgments

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2012R1A6A3A01019025 and 2012R1A1A2004577).

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Correspondence to Eui-Suk Jeong.

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This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Jeong, D., Seo, J., Heo, S. et al. Tumor necrosis factor-alpha deficiency impairs host defense against Streptococcus pneumoniae. Lab Anim Res 31, 78–85 (2015). https://doi.org/10.5625/lar.2015.31.2.78

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Keywords

  • Tumor necrosis factor-alpha knockout
  • Streptococcus pneumoniae
  • pneumonia