| First Author | Zhang X | Year | 2011 |
| Journal | Infect Immun | Volume | 79 |
| Issue | 1 | Pages | 527-41 |
| PubMed ID | 20974829 | Mgi Jnum | J:167554 |
| Mgi Id | MGI:4868537 | Doi | 10.1128/IAI.00590-10 |
| Citation | Zhang X, et al. (2011) Interleukin-1 receptor signaling is required to overcome the effects of pertussis toxin and for efficient infection- or vaccination-induced immunity against Bordetella pertussis. Infect Immun 79(1):527-41 |
| abstractText | Interleukin-1 receptor-deficient (IL-1R(-/-)) mice are healthy despite being colonized by commensal microbes but are defective in defenses against specific pathogens, suggesting that IL-1R-mediated effects contribute to immune responses against specific pathogenic mechanisms. To better define the role of IL-1R in immunity to respiratory infections, we challenged IL-1R(-/-) mice with Bordetella pertussis and Bordetella parapertussis, the causative agents of whooping cough. Following inoculation with B. pertussis, but not B. parapertussis, IL-1R(-/-) mice showed elevated bacterial numbers and more extensive inflammatory pathology than wild-type mice. Acellular B. pertussis vaccines were not efficiently protective against B. pertussis in IL-1R(-/-) mice. B. pertussis-stimulated dendritic cells from IL-1R(-/-) mice produced higher levels of tumor necrosis factor alpha (TNF-alpha) and IL-6 than wild-type cells. Moreover, elevated levels of gamma interferon (IFN-gamma) and TNF-alpha but lower levels of IL-10 were detected during B. pertussis infection in IL-1R(-/-) mice. Since B. parapertussis did not cause severe disease in IL-1R(-/-) mice, we hypothesized that the extreme requirement for IL-1R involves pertussis toxin (Ptx), which is expressed only by B. pertussis. An isogenic Ptx-deficient B. pertussis strain had only a modest phenotype in wild-type mice but was completely defective in causing lethal disease in IL-1R(-/-) mice, indicating that the particular virulence of B. pertussis in these mice requires Ptx. Ptx contributes to IL-1beta induction by B. pertussis, which is involved in IL-10 induction through IL-1R signaling. IL-10 treatment reduced B. pertussis numbers in IL-1R(-/-) mice, suggesting that the lower IL-10 responses partially account for the uncontrolled inflammation and bacterial growth in these mice. |
