Published ahead of print on July 10, 2003, doi:10.1165/rcmb.2003-0156OC Am. J. Respir. Cell Mol. Biol., Volume 30, Number 1, January 2004, 109-117 A more recent version of this article appeared on January 1, 2004
Submitted on May 1, 2003 Role of Interleukin-4 in Resistance to Cryptococcus neoformans InfectionRebecca Blackstock1* and Juneann W Murphy11 Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA * To whom correspondence should be addressed. E-mail: becky-blackstock{at}ouhsc.edu.
The role of IL-4 in cryptococcal disease was studied in IL-4 knockout (IL-4KO) and wildtype (WT) mice infected with Cryptococcus neoformans isolates that vary widely in their virulence. Delayed-type hypersensitivity (DTH) 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 down-regulated 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 CFU 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 DTH responses after intravenous infection with 184A and were more resistant to infection compared to WT mice. Increased expression of IL-5 with decreased INF-
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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 INF-
