Interleukin 18 restores defective Th1 immunity to Candida albicans in caspase 1-deficient mice.
Caspase 1, formerly designated interleukin 1beta (IL-1beta)-converting enzyme, processes pro-IL-1beta and pro-IL-18 to yield active cytokines that play a pivotal role in inflammation and cell activation. We show here the effect of caspase 1 deficiency on the inflammatory and adaptive immune responses to the fungus Candida albicans. Caspase 1 deficiency did not affect susceptibility to primary systemic infection with the fungus, as revealed by survival and fungal growth. However, Th1-mediated resistance to reinfection was greatly impaired in caspase 1-deficient mice, and this correlated with low-level production of IL-12 and gamma interferon. Early in infection, production of these cytokines and that of tumor necrosis factor alpha, IL-6, and, interestingly, IL-1beta occurred normally in caspase 1-deficient mice, while that of IL-18 was severely impaired. Exogenous administration of IL-18, more than IL-12, restored the Th1-mediated resistance to the infection. We conclude that, while caspase 1 is not indispensable for release of mature IL-1beta in candidiasis, the caspase 1-dependent production of IL-18 may represent an important and novel pathway for the expression of sustained Th1 reactivity to the fungus.
Mencacci
A
A
Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, 06122 Perugia, Italy.
Bacci
A
A
Cenci
E
E
Montagnoli
C
C
Fiorucci
S
S
Casagrande
A
A
Flavell
R A
RA
Bistoni
F
F
Romani
L
L
D000818:Animals; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology; D020170:Caspase 1 / Q000172:deficiency / Q000502:physiology*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D020382:Interleukin-18 / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology
D020382:Interleukin-18; D018664:Interleukin-12; D007371:Interferon-gamma; D020170:Caspase 1