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.
Zhang
Xuqing
X
Department of Veterinary and Biomedical Sciences, Pennsylvania State University, 115 Henning Building, University Park, PA 16802, USA.
Hester
Sara E
SE
Kennett
Mary J
MJ
Karanikas
Alexia T
AT
Bendor
Liron
L
Place
David E
DE
Harvill
Eric T
ET
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