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Infection and Immunity, October 2003, p. 5756-5764, Vol. 71, No. 10
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.10.5756-5764.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Parenchymal Organ, and Not Splenic, Immunity Correlates with Host Survival during Disseminated Candidiasis

Brad Spellberg,1 Douglas Johnston,1 Quynh Trang Phan,1 John E. Edwards Jr.,1,2 Samuel W. French,2,3 Ashraf S. Ibrahim,1,2 and Scott G. Filler1,2*

Departments of Medicine,1 Pathology, Research and Education Institute at Harbor-UCLA Medical Center, Torrance,3 the School of Medicine, University of California, Los Angeles, Los Angeles, California2

Received 6 May 2003/ Returned for modification 8 July 2003/ Accepted 17 July 2003

We examined the relationship between host survival and renal and splenic immune responses in a murine model of hematogenously disseminated candidiasis. Male BALB/c mice were infected via tail vein injection with wild-type C. albicans or with an isogenic, {Delta}efg1/{Delta}efg1 hypha-deficient mutant. Host survival, organ fungal burden, intracellular cytokine content of splenic and kidney lymphocytes, and whole-organ cytokine profiles were determined. Wild-type C. albicans induced type 2 splenocyte responses with both nonfatal and fatal inocula. In the kidney, conversely, wild-type inocula causing no or low mortality induced type 1 responses and 100% fatal inocula induced type 2 or interleukin-10 (IL-10)-dominant responses. Hypha-deficient mutant C. albicans caused no or low mortality while inducing type 1 responses in both the spleen and kidney. To our knowledge, this is the first demonstration that host survival during systemic infection correlates with the type of immune response engendered in a nonlymphoid, parenchymal organ and not with the response in the spleen. Furthermore, the results provide in vivo confirmation that hyphal formation by C. albicans induces type 2 or IL-10-dominant host responses in tissues.

* Corresponding author. Mailing address: Division of Infectious Diseases, Harbor-UCLA Research and Education Institute, 1124 W. Carson St., Torrance, CA 90502. Phone: (310) 222-3813. Fax: (310) 782-2016. E-mail: sfiller{at}ucla.edu.

Editor: T. R. Kozel

Infection and Immunity, October 2003, p. 5756-5764, Vol. 71, No. 10
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.10.5756-5764.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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