Protection against cryptococcosis by using a murine gamma interferon-producing Cryptococcus neoformans strain.
We evaluated cell-mediated immune (CMI) responses in mice given a pulmonary infection with a Cryptococcus neoformans strain engineered to produce the Th1-type cytokine gamma interferon (IFN-gamma). Mice given a pulmonary infection with an IFN-gamma-producing C. neoformans strain were able to resolve the primary infection and demonstrated complete (100%) protection against a second pulmonary challenge with a pathogenic C. neoformans strain. Pulmonary cytokine analyses showed that Th1-type/proinflammatory cytokine and chemokine expression were significantly higher and Th2-type cytokine expression was significantly lower in mice infected with the IFN-gamma-producing C. neoformans strain compared to wild-type-infected mice. This increased pulmonary Th1-type cytokine expression was also associated with significantly lower pulmonary fungal burden and significantly higher pulmonary leukocyte and T-lymphocyte recruitment in mice infected with the IFN-gamma-producing C. neoformans strain compared to wild-type-infected mice. Our results demonstrate that pulmonary infection of mice with a C. neoformans strain expressing IFN-gamma results in the stimulation of local Th1-type anti-cryptococcal CMI responses and the development of protective host immunity against future pulmonary cryptococcal infections. The use of fungi engineered to produce host cytokines is a novel method to study immune responses to infection and may be useful in developing vaccine strategies in humans.
Wormley
Floyd L
FL
Department Biology, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249-0062, USA. floyd.wormley@utsa.edu
Perfect
John R
JR
Steele
Chad
C
Cox
Gary M
GM
D000818:Animals; D003453:Cryptococcosis / Q000276:immunology* / Q000517:prevention & control*; D003455:Cryptococcus neoformans / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis*; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C
D007371:Interferon-gamma