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

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.

Difference in Resistance to Streptococcus pneumoniae Infection in Mice / 한국실험동물학회지

Streptococcus pneumoniae is a major pathogen that causes various diseases, including pneumonia and sepsis, as millions of people suffer from S. pneumoniae infection worldwide. To better understand the immune and inflammatory responses to S. pneumoniae, we produced murine models. To investigate the differences between intranasal and intratracheal infection, BALB/c mice were infected with S. pneumoniae D39 intranasally or intratracheally. Mice showed no significant differences in survival rates, body weight changes, and bacterial loads. To investigate resistance and susceptibility among mouse strains, BALB/c, C57BL/6J, tumor necrosis factor-alpha (TNF-alpha) knockout, and interleukin-10 (IL-10) knockout mice were infected with S. pneumoniae D39 via intranasal or intravenous routes. In this study, BALB/c and C57BL/6J mice were resistant, IL-10 knockout mice were intermediate, and TNF-alpha knokout mice were susceptible to S. pneumoniae infection. These data show that intranasal and intratracheal infection induced similar results after S. pneumoniae infection, and the genetic background of mice must be considered when studying S. pneumoniae infection in vivo.

A Novel Model for Human Atopic Dermatitis: Application of Repeated DNCB Patch in BALB/c Mice, in Comparison with NC/Nga Mice / 한국실험동물학회지

The various murine models have contributed to the study of human atopic dermatitis (AD). However limitations of the models involve low reproducibility and long time to develop AD. In an attempt to overcome these limitations and establish an atopic dermatitis murine model, we repeated the application of 2, 4-dinitrochlorobenzene (DNCB) patch in NC/Nga and BALB/c mice, which has advantages in reproduction and cost. For the sensitization, a 1 cm2 gauze-attached patch, where 1% or 0.2% DNCB was periodically attached on the back of NC/Nga and BALB/c mice. To estimate how homologous our model was with human atopic dermatitis, clinical, histological and immunological alterations were evaluated. Both strains showed severe atopic dermatitis, increase in subiliac lymph node weight, mast cells, epidermal hyperplasia and serum IgE levels. Though both exhibited a high IL-4/IFN-gamma and IL-4/TNF-beta ratio in the expression of mRNA, the shifting of DNCB-treated BALB/c mice was increased to more than double that of NC/Nga mice. These results suggest that our DNCB patched model using BALB/c mice were more suitable than NC/Nga mice in demonstrating the immune response. We anticipate that our novel model may be successfully used for pathogenesis of atopic dermatitis and assessment of therapeutic approaches.