This Article Full Text Full Text (PDF) All Versions of this Article: 2003-0156OCv1 30/1/109    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Blackstock, R. Articles by Murphy, J. W. Search for Related Content PubMed PubMed Citation Articles by Blackstock, R. Articles by Murphy, J. W.

Role of Interleukin-4 in Resistance to Cryptococcus neoformans Infection

Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma

Address correspondence to: Rebecca Blackstock, Ph.D., Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, P.O. Box 26901, Oklahoma City, OK 73190. E-mail: becky-blackstock{at}ouhsc.edu

The role of interleukin (IL)-4 in cryptococcal disease was studied in IL-4 knockout (IL-4KO) and wild-type (WT) mice infected with Cryptococcus neoformans isolates that vary widely in their virulence. Delayed-type hypersensitivity responses were reduced in IL-4KO mice following primary infection with either isolate. Splenic T helper 1 (Th1) cytokine responses were increased in the IL-4KO mice infected with the weakly virulent isolate (184A) but did not change during infection with the highly virulent isolate (NU-2). Th2 cytokine responses (IL-5, IL-10) were downregulated in the IL-4KO mice infected with either isolate. Survival after primary infection with either isolate was not influenced by the absence of IL-4. Fewer colony-forming units were found in the lungs of 184A-infected, IL-4KO mice as compared to WT mice, suggesting that some immunity had developed. IL-4KO mice, primed with small doses of cryptococcal antigen (CneF), had significantly enhanced delayed-type hypersensitivity responses after intravenous infection with 184A and were more resistant to infection compared with WT mice. Increased expression of IL-5 with decreased interferon- contributed to the inability of primed WT mice to resist infection with 184A. Enhanced immunity in the primed IL-4KO mice was reflected in a more moderate increase in IL-5 and IL-10 with maintenance of interferon- levels.

Abbreviations: colony-forming units, cfu • cell-mediated immunity, CMI • cryptococcal culture filtrate antigen, CneF • delayed-type hypersensitivity, DTH • enzyme-linked immunosorbent assay, ELISA • fetal bovine serum, FBS • Hanks' balanced salt solution, HBSS • interferon-, IFN- • interleukin, IL • IL-4–deficient mice, IL-4KO • sterile physiological saline solution, SPSS • T helper 1, Th1 • T helper 2, Th2 • wild-type, WT

This article has been cited by other articles:

				Y. Zhang, F. Wang, K. C. Tompkins, A. McNamara, A. V. Jain, B. B. Moore, G. B. Toews, G. B. Huffnagle, and M. A. Olszewski Robust Th1 and Th17 Immunity Supports Pulmonary Clearance but Cannot Prevent Systemic Dissemination of Highly Virulent Cryptococcus neoformans H99 Am. J. Pathol., December 1, 2009; 175(6): 2489 - 2500. [Abstract] [Full Text] [PDF]

				M. A. Kleinschek, U. Muller, N. Schutze, R. Sabat, R. K. Straubinger, W. M. Blumenschein, T. McClanahan, R. A. Kastelein, and G. Alber Administration of IL-23 engages innate and adaptive immune mechanisms during fungal infection Int. Immunol., November 30, 2009; (2009) dxp117v1. [Abstract] [Full Text] [PDF]

				K. Voelz, D. A. Lammas, and R. C. May Cytokine Signaling Regulates the Outcome of Intracellular Macrophage Parasitism by Cryptococcus neoformans Infect. Immun., August 1, 2009; 77(8): 3450 - 3457. [Abstract] [Full Text] [PDF]

				J. J. Osterholzer, R. Surana, J. E. Milam, G. T. Montano, G.-H. Chen, J. Sonstein, J. L. Curtis, G. B. Huffnagle, G. B. Toews, and M. A. Olszewski Cryptococcal Urease Promotes the Accumulation of Immature Dendritic Cells and a Non-Protective T2 Immune Response within the Lung Am. J. Pathol., March 1, 2009; 174(3): 932 - 943. [Abstract] [Full Text] [PDF]

				W. Stenzel, U. Muller, G. Kohler, F. L. Heppner, M. Blessing, A. N.J. McKenzie, F. Brombacher, and G. Alber IL-4/IL-13-Dependent Alternative Activation of Macrophages but Not Microglial Cells Is Associated with Uncontrolled Cerebral Cryptococcosis Am. J. Pathol., February 1, 2009; 174(2): 486 - 496. [Abstract] [Full Text] [PDF]

				U. Muller, W. Stenzel, G. Kohler, C. Werner, T. Polte, G. Hansen, N. Schutze, R. K. Straubinger, M. Blessing, A. N. J. McKenzie, et al. IL-13 Induces Disease-Promoting Type 2 Cytokines, Alternatively Activated Macrophages and Allergic Inflammation during Pulmonary Infection of Mice with Cryptococcus neoformans J. Immunol., October 15, 2007; 179(8): 5367 - 5377. [Abstract] [Full Text] [PDF]

				L. E. Yauch, M. K. Mansour, S. Shoham, J. B. Rottman, and S. M. Levitz Involvement of CD14, Toll-Like Receptors 2 and 4, and MyD88 in the Host Response to the Fungal Pathogen Cryptococcus neoformans In Vivo Infect. Immun., September 1, 2004; 72(9): 5373 - 5382. [Abstract] [Full Text] [PDF]