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Infection and Immunity, September 2000, p. 5126-5131, Vol. 68, No. 9
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Interleukin 18 Restores Defective Th1 Immunity to Candida albicans in Caspase 1-Deficient Mice

Antonella Mencacci,1 Angela Bacci,1 Elio Cenci,1 Claudia Montagnoli,1 Sabrina Fiorucci,1 Andrea Casagrande,1 Richard A. Flavell,2 Francesco Bistoni,1 and Luigina Romani1,*

Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, 06122 Perugia, Italy,1 and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 065102

Received 22 February 2000/Returned for modification 1 May 2000/Accepted 20 June 2000

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.

* Corresponding author. Mailing address: Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, 06122 Perugia, Italy. Phone and fax: 39-075-5857411. E-mail: lromani{at}unipg.it.

Infection and Immunity, September 2000, p. 5126-5131, Vol. 68, No. 9
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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