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Oroesophageal candidiasis is lethal for transgenic mice with combined natural killer and T-cell defects
E Balish1, T Warner, C J Pierson
1Department of Surgery, University of Wisconsin Medical School, Madison 53706, USA. balish@surgery.wisc.edu
Abstract:
Germfree transgenic epsilon 26 (Tgepsilon26) mice, which express the full-length human CD3epsilon gene, have combined defects in natural killer (NK) cells and T cells were found to be extremely susceptible to oroesophageal (palate, tongue, esophagus) and gastric (cardia-antrum section) candidiasis. The gnotobiotic Tgepsilon26 mice die, apparently from severe oroesophageal candidiasis, within 2-4 weeks after their alimentary tracts are colonized with Candida albicans. The Tgepsilon26 mice manifest resistance to acute systemic candidiasis (intravenous injection) and to systemic candidiasis of endogenous origin for the first 2 weeks after their alimentary tracts are colonized with C. albicans. Granulocyte depletion data suggest that granulocytes, in the absence of functional NK cells and T cells, can protect Tgepsilon26 mice from acute systemic candidiasis and from systemic candidiasis of endogenous origin, for at least 14 days after alimentary tract colonization. Granulocytes and macrophages, in the absence of NK cells and T cells, are unable to protect Tgepsilon26 mice from lethal oroesophageal candidiasis and systemic candidiasis of endogenous origin which was evident in moribund Tgepsilon26 mice 2-4 weeks after colonization. Thus, non-T cells (i.e., NK cells) and T cells play important roles in resistance to oroesophageal and systemic (acute and of endogenous origin) candidiasis.
Insights
Germfree mice with defects in natural killer (NK) and T cells are highly susceptible to Candida albicans infections in the esophagus and stomach. These immune cells are crucial for preventing severe candidiasis.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Transgenic mice models are essential for studying host-pathogen interactions.
- Candida albicans is an opportunistic fungal pathogen that can cause severe infections in immunocompromised individuals.
- Natural killer (NK) cells and T cells play critical roles in the immune response against fungal infections.
Purpose of the Study:
- To investigate the role of NK cells and T cells in host defense against Candida albicans.
- To determine the susceptibility of germfree transgenic epsilon 26 (Tgepsilon26) mice with combined NK and T cell defects to candidiasis.
Main Methods:
- Utilized germfree transgenic epsilon 26 (Tgepsilon26) mice expressing the human CD3epsilon gene.
- Colonized the alimentary tracts of Tgepsilon26 mice with Candida albicans.
- Assessed susceptibility to oroesophageal, gastric, and systemic candidiasis.
- Performed granulocyte depletion experiments to evaluate the role of granulocytes and macrophages.
Main Results:
- Tgepsilon26 mice exhibited extreme susceptibility to oroesophageal and gastric candidiasis, succumbing within 2-4 weeks post-colonization.
- These mice showed resistance to acute systemic candidiasis for the first 2 weeks.
- Granulocytes and macrophages alone could not prevent lethal oroesophageal and systemic candidiasis in the absence of NK and T cells.
Conclusions:
- NK cells and T cells are vital for effective host resistance against oroesophageal and systemic candidiasis.
- Combined defects in NK and T cells lead to severe susceptibility to mucosal and systemic candidiasis caused by Candida albicans.
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