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

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

• Jeong DG
• Seo JH
• Heo SH
• Choi YK
• Jeong ES

• KMID: 2053681
• DOI: http://doi.org/10.5625/lar.2015.31.2.78

Abstract

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

Keyword

Tumor necrosis factor-alpha knockout; Streptococcus pneumoniae; pneumonia

MeSH Terms

Animals
Bacterial Load
Body Weight
Humans
Inflammation
Interferon-gamma
Interleukin-10
Lung
Mice
Pneumonia
Pneumonia, Pneumococcal
Spleen
Streptococcus pneumoniae*
Survival Rate
Tumor Necrosis Factor-alpha*
Interferon-gamma
Interleukin-10
Tumor Necrosis Factor-alpha

Figure

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  Figure 1 Survival rate (A) and changes in body weight (B) of WT and TNF-α KO mice after intranasal S. pneumoniae infection. The infected TNF-α KO mice had significantly lower survival rates and lost more weight than WT mice. Values presented are means±SD. *P<0.05 and **P<0.01 compared with WT mice.

• 

  Figure 2 Bacterial counts in the lungs (A) and blood (B) of WT and TNF-α KO mice after intranasal S. pneumoniae infection. The TNF-α KO mice exhibited bacterial counts in the lungs and blood that were significantly increased compared with those in WT mice. Values presented are means±SD. *P<0.05 and **P<0.01 compared with WT mice.

• 

  Figure 3 Histopathological analysis of lungs from WT and TNF-α KO mice after intranasal S. pneumoniae infection. The lungs of WT (A, C, E) and TNF-α KO (B, D) mice at 0 (A, B), 48 (C, D), and 72 h (E) post-infection. Sections were stained with H&E. The degree of pneumonia was scored and expressed as the means±SD (F).

• 

  Figure 4 Histopathological analysis of spleen tissue from WT and TNF-α KO mice after intranasal S. pneumoniae infection. The spleens of WT (A, C, E) and TNF-α KO (B, D) mice at 0 (A, B), 48 (C, D), and 72 h (E) post-infection. Sections were stained with H&E. The degree of white pulp depletion was scored and expressed as the means±SD (F). *P<0.05 compared with WT mice.

• 

  Figure 5 Apoptotic cells in the splenic white pulp of WT and TNF-α KO mice after intranasal S. pneumoniae infection. WT (A, C, E) and TNF-α KO (B, D) mice at 0 (A, B), 48 (C, D), and 72 h (E) post-infection. Apoptotic cells were quantified and expressed as the means±SD/mm2 (F). **P<0.01 compared with WT mice.

• 

  Figure 6 Cytokine levels in the serum of WT and TNF-α KO mice after intranasal S. pneumoniae infection. IFN-γ (A), IL-12p70 (B) and IL-10 (C) levels in the serum of WT and TNF-α KO mice were measured using ELISAs and values expressed as the means±SD. *P<0.05 and **P<0.01 compared with WT mice.

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