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Infect Immun, April 1998, p. 1708-1717, Vol. 66, No. 4
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Characteristics of Invasive Candidiasis in Gamma Interferon- and Interleukin-4-Deficient Mice: Role of Macrophages in Host Defense against Candida albicans

Rita Káposzta,1 Peter Tree,2 László Maródi,1 and Siamon Gordon2,*

Department of Pediatrics, University School of Medicine Debrecen, H-4012 Debrecen, Hungary,1 and Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom2

Received 12 September 1997/Returned for modification 3 November 1997/Accepted 20 January 1998

Murine models of invasive candidiasis were used to study the in vivo importance of gamma interferon (IFN-gamma ) and interleukin-4 (IL-4) in host defense against Candida albicans and to characterize the tissue inflammatory reactions, with special reference to macrophages (Mphi ). Knockout (KO) IFN-gamma -deficient (GKO) and IL-4-deficient (IL-4 KO) and C57BL/6 parental mouse strains were challenged intraperitoneally with 108 C. albicans blastoconidia. Survival of GKO mice was significantly lower (16.7%) than that of C57BL/6 control (55.5%) and IL-4 KO (61.1%) animals, but was not correlated with the extent of organ colonization. Immunohistological analysis with a panel of myeloid and lymphoid markers revealed multiple renal abscesses, myocarditis, hepatitis, meningoencephalitis, and pneumonia in each strain, with a dominant presence of Mphi . In the absence of IFN-gamma , C. albicans induced striking changes in the phenotype of alveolar Mphi and extensive perivascular lymphoid infiltrates in the lung. Impairment in nitric oxide production by peritoneal Mphi was shown only in GKO mice, and they produced Candida-specific immunoglobulin G (IgG), IgM, IgA, and IgG subclasses in lower titers. Our in vivo studies with KO mice elucidate a critical role for IFN-gamma , but not IL-4, in host defense against C. albicans.

* Corresponding author. Mailing address: Sir William Dunn School of Pathology, South Parks Rd., Oxford OX1 3RE, United Kingdom. Phone: 1865-275-534. Fax: 1865-275-515. E-mail: christine.holt{at}path.ox.ac.uk.




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