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

Jeong DG, Seo JH, Heo SH, Choi YK, Jeong ES - Lab Anim Res (2015)

Bottom Line: Tumor necrosis factor-alpha (TNF-α) is a pro-inflammatory cytokine that activates immune responses against infection, invasion, injury, or inflammation.Interferon-gamma (IFN-γ), IL-12p70 and IL-10 levels in serum were significantly increased in TNF-α KO mice.Our findings suggest that TNF-α plays a critical role in protecting the host from systemic S. pneumoniae infection.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, Seoul, Korea.

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.

No MeSH data available.


Related in: MedlinePlus

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.
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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.

Mentions: We examined lung and spleen tissue sections that had been stained with H&E for histopathological analysis. In lung sections, intra-alveolar inflammation, bronchitis, edema, and endothelialitis were observed, with the degree of pneumonia scored (Figure 3). No significant differences were observed between WT and TNF-α KO mice. These results reflect those in BAL fluid with respect to differential cell counts. In the spleen sections, those from TNF-α KO mice showed severe white pulp depletion at 48 h post-infection while spleens from WT mice had a normal appearance until 72 h post-infection (Figure 4). These results suggest that intranasal S. pneumoniae D39 infection results in systemic damage as opposed to local lung damage. Because severe white pulp depletion was observed in the spleens of TNF-α KO mice, the degree of apoptosis in white pulp was evaluated. Apoptotic cells were stained using TUNEL assays and the number of apoptotic cells counted. The white pulp of TNF-α KO mice contained a significantly increased number of apoptotic cells at 48 h post-infection. The WT mice did not exhibit such an increase until 72 h post-infection (Figure 5).


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

Jeong DG, Seo JH, Heo SH, Choi YK, Jeong ES - Lab Anim Res (2015)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490149&req=5

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.
Mentions: We examined lung and spleen tissue sections that had been stained with H&E for histopathological analysis. In lung sections, intra-alveolar inflammation, bronchitis, edema, and endothelialitis were observed, with the degree of pneumonia scored (Figure 3). No significant differences were observed between WT and TNF-α KO mice. These results reflect those in BAL fluid with respect to differential cell counts. In the spleen sections, those from TNF-α KO mice showed severe white pulp depletion at 48 h post-infection while spleens from WT mice had a normal appearance until 72 h post-infection (Figure 4). These results suggest that intranasal S. pneumoniae D39 infection results in systemic damage as opposed to local lung damage. Because severe white pulp depletion was observed in the spleens of TNF-α KO mice, the degree of apoptosis in white pulp was evaluated. Apoptotic cells were stained using TUNEL assays and the number of apoptotic cells counted. The white pulp of TNF-α KO mice contained a significantly increased number of apoptotic cells at 48 h post-infection. The WT mice did not exhibit such an increase until 72 h post-infection (Figure 5).

Bottom Line: Tumor necrosis factor-alpha (TNF-α) is a pro-inflammatory cytokine that activates immune responses against infection, invasion, injury, or inflammation.Interferon-gamma (IFN-γ), IL-12p70 and IL-10 levels in serum were significantly increased in TNF-α KO mice.Our findings suggest that TNF-α plays a critical role in protecting the host from systemic S. pneumoniae infection.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, Seoul, Korea.

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.

No MeSH data available.


Related in: MedlinePlus