Role of interleukin-4 in resistance to Cryptococcus neoformans infection.
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-gamma 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-gamma levels.
Blackstock
Rebecca
R
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, P.O. Box 26901, Oklahoma City, OK 73190, USA. becky-blackstock@ouhsc.edu
Murphy
Juneann W
JW
D000818:Animals; D003453:Cryptococcosis / Q000276:immunology / Q000503:physiopathology*; D003455:Cryptococcus neoformans / Q000276:immunology / Q000302:isolation & purification* / Q000472:pathogenicity; D015536:Down-Regulation; D005260:Female; D006968:Hypersensitivity, Delayed; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D015847:Interleukin-4; D007371:Interferon-gamma