title: 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.
authors.affiliation: Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, Seoul, Korea.
authors.forename: Dong-Gu
authors.initials: DG
authors.lastname: Jeong
authors.affiliation: Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, Seoul, Korea. ; Laboratory Animal Facility, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Seo
authors.affiliation: Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, Seoul, Korea. ; Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Seung-Ho
authors.initials: SH
authors.lastname: Heo
authors.affiliation: Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, Seoul, Korea.
authors.forename: Yang-Kyu
authors.initials: YK
authors.lastname: Choi
authors.affiliation: Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, Seoul, Korea. ; Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Korea.
authors.forename: Eui-Suk
authors.initials: ES
authors.lastname: Jeong
keywords: Streptococcus pneumoniae; Tumor necrosis factor-alpha knockout; pneumonia