Interleukin-1 receptor signaling is required to overcome the effects of pertussis toxin and for efficient infection- or vaccination-induced immunity against Bordetella pertussis.
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-α) and IL-6 than wild-type cells. Moreover, elevated levels of gamma interferon (IFN-γ) and TNF-α 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-1β 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.
Department of Veterinary and Biomedical Sciences, Pennsylvania State University, 115 Henning Building, University Park, PA 16802, USA.
Xuqing
X
Zhang
Sara E
SE
Hester
Mary J
MJ
Kennett
Alexia T
AT
Karanikas
Liron
L
Bendor
David E
DE
Place
Eric T
ET
Harvill
D000818:Animals; D042483:Bordetella parapertussis / Q000276:immunology; D001886:Bordetella pertussis / Q000276:immunology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D037342:Pertussis Toxin / Q000633:toxicity*; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013995:Time
D007375:Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D037342:Pertussis Toxin