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.

journal_name

Eur J Immunol

authors

Netea MG,Vonk AG,van den Hoven M,Verschueren I,Joosten LA,van Krieken JH,van den Berg WB,Van der Meer JW,Kullberg BJ

doi

10.1002/eji.200323737

keywords:

subject

Has Abstract

pub_date

2003-12-01 00:00:00

pages

3409-17

issue

12

eissn

0014-2980

issn

1521-4141

journal_volume

33

pub_type

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