title: Differential role of IL-18 and IL-12 in the host defense against disseminated Candida albicans infection.
abstract: IFN-gamma plays a crucial role in the defense against infection with Candida albicans. Since IL-18 and IL-12 are strong stimuli of IFN-gamma production, we investigated whether endogenous IL-18 and IL-12 are involved in the host defense during disseminated candidiasis. IL-18 knockout (IL-18-/-) mice, but not IL-12-/- mice, displayed an increased mortality due to C. albicans infection, accompanied by a decreased clearance of the yeasts from the kidneys late during the course of infection. Histopathology of the organs, combined with phagocyte recruitment experiments, showed a decreased influx of monocytes at the sites of Candida infection, mainly in the IL-18-/- mice. Whereas production of the chemokine KC was decreased in both IL-18-/- and IL-12-/- mice, MIP-2 production was deficient only in IL-18-/- animals, which may explain the differences in phagocyte recruitment. In addition, although IFN-gamma production capacity, as a parameter of the Th1-protective immunity, was reduced by 65 to 80% in the IL-12-/- mice, this defect was even more pronounced in the IL-18-/- mice (85 to 95% down-modulation). In conclusion, the anticandidal effects of endogenous IL-18 are mediated late during the infection by assuring a proper IFN-gamma response and promoting the infiltration of the site of infection by monocytes.
authors.affiliation: Department of Medicine, University Medical Center St. Radboud, Nijmegen, Nijmegen, The Netherlands.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.forename: Alieke G
authors.initials: AG
authors.lastname: Vonk
authors.forename: Mabel
authors.initials: M
authors.lastname: van den Hoven
authors.forename: Ineke
authors.initials: I
authors.lastname: Verschueren
authors.forename: Leo A
authors.initials: LA
authors.lastname: Joosten
authors.forename: Johan H
authors.initials: JH
authors.lastname: van Krieken
authors.forename: Wim B
authors.initials: WB
authors.lastname: van den Berg
authors.forename: Jos W M
authors.initials: JW
authors.lastname: Van der Meer
authors.forename: Bart Jan
authors.initials: BJ
authors.lastname: Kullberg
mesh_terms: D000818:Animals; D002177:Candidiasis / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000502:physiology*; D020382:Interleukin-18 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis
chemical_list: D016207:Cytokines; D020382:Interleukin-18; D018664:Interleukin-12; D007371:Interferon-gamma