Interleukin-1 receptor signaling is required to overcome the effects of pertussis toxin and for efficient infection-or vaccination-induced immunity against bordetella pertussis

Xuqing Zhang, Sara E. Hester, Mary J. Kennett, Alexia T. Karanikas, Liron Bendor, David E. Place, Eric T. Harvill

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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. pertussisstimulated dendritic cells from IL-1R -/- mice produced higher levels of tumor necrosis factor alpha (TNF-γ) and IL-6 than wild-type cells. Moreover, elevated levels of gamma interferon (IFN-α) and TNF-γ 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-1 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.

Original languageEnglish (US)
Pages (from-to)527-541
Number of pages15
JournalInfection and Immunity
Volume79
Issue number1
DOIs
StatePublished - Jan 2011

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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