期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 13, 期 4, 页码 490-498出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2012.05.008
关键词
Aryl hydrocarbon receptor; Streptococcus pneumoniae; Natural antibodies; iNKT cells; Host-protection; TCDD
资金
- NIH from the National Institute of Allergy and Infectious Disease [R15-AI82403-1]
- Washington State University Foundation and Office of Research
- American Society for Pharmacology and Experimental Therapeutics
- WSU College of Pharmacy
Streptococcus pneumoniae is a primary cause of invasive bacterial infection and pneumonia and is one of the leading causes of death worldwide. In prior studies we showed that pre-treating mice with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent agonist of the aryl hydrocarbon receptor (AhR), protects against S. pneumoniae-induced mortality and reduces pulmonary bacterial burden. The current studies were conducted to help elucidate the mechanism for this protective effect, and to characterize the response in the lung during the first 10 h following infection. C57BI/6 mice were treated with TCDD one day prior to intranasal infection with serotype 3 S. pneumoniae. Monitoring of bacteria in the lung airways revealed that bacterial growth was inhibited in the TCDD-treated animals within 10 h of infection. To address the mechanism of this rapid protective response, macrophages, neutrophils, and invariant Natural Killer T (iNKT) cells were quantified, and levels of natural antibodies produced by B-1 B cells were evaluated. Functional assays addressed whether AhR activation reduced the capacity of lung epithelial cells to bind bacteria, and whether TCDD treatment enhanced production of antimicrobial agents in the lung or blood. None of the hypothesized mechanisms was able to explain the protective effect. Finally, the exposure paradigm was manipulated to test whether administration of TCDD after instillation of the bacteria was also protective. Results showed that TCDD must be administered in advance of exposure to bacteria, suggesting that the lung environment is rendered inhospitable to the pathogens. (C) 2012 Elsevier B.V. All rights reserved.
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