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

Lab Anim Res. 2015 Jun;31(2):78-85. doi: 10.5625/lar.2015.31.2.78. Epub 2015 Jun 26.

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

Jeong DG1, Seo JH2, Heo SH3, Choi YK1, Jeong ES4.

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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.

KEYWORDS:

Streptococcus pneumoniae; Tumor necrosis factor-alpha knockout; pneumonia

PMID: 26155202 [PubMed] PMCID: PMC4490149