PMID- 26155202 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20150709 LR - 20201001 IS - 1738-6055 (Print) IS - 2233-7660 (Electronic) IS - 1738-6055 (Linking) VI - 31 IP - 2 DP - 2015 Jun TI - Tumor necrosis factor-alpha deficiency impairs host defense against Streptococcus pneumoniae. PG - 78-85 LID - 10.5625/lar.2015.31.2.78 [doi] AB - 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. FAU - Jeong, Dong-Gu AU - Jeong DG AD - Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, Seoul, Korea. FAU - Seo, Jin-Hee AU - Seo JH AD - 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. FAU - Heo, Seung-Ho AU - Heo SH AD - 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. FAU - Choi, Yang-Kyu AU - Choi YK AD - Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, Seoul, Korea. FAU - Jeong, Eui-Suk AU - Jeong ES AD - Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, Seoul, Korea. ; Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Korea. LA - eng PT - Journal Article DEP - 20150626 PL - England TA - Lab Anim Res JT - Laboratory animal research JID - 101560684 PMC - PMC4490149 OTO - NOTNLM OT - Streptococcus pneumoniae OT - Tumor necrosis factor-alpha knockout OT - pneumonia COIS- Conflict of interests: The authors declare that there is no financial conflict of interests to publish these results. EDAT- 2015/07/15 06:00 MHDA- 2015/07/15 06:01 PMCR- 2015/06/01 CRDT- 2015/07/09 06:00 PHST- 2015/04/23 00:00 [received] PHST- 2015/05/21 00:00 [revised] PHST- 2015/05/31 00:00 [accepted] PHST- 2015/07/09 06:00 [entrez] PHST- 2015/07/15 06:00 [pubmed] PHST- 2015/07/15 06:01 [medline] PHST- 2015/06/01 00:00 [pmc-release] AID - 10.5625/lar.2015.31.2.78 [doi] PST - ppublish SO - Lab Anim Res. 2015 Jun;31(2):78-85. doi: 10.5625/lar.2015.31.2.78. Epub 2015 Jun 26.