Susceptibility of gnotobiotic transgenic mice (Tgepsilon26) with combined deficiencies in natural killer cells and T cells to wild-type and hyphal signalling-defective mutants of Candida albicans.
Germfree transgenic epsilon 26 mice (Tgepsilon26), deficient in natural killer cells and T cells, were colonized (alimentary tract) with Candida albicans wild-type or each of two hyphal transcription factor signalling mutant strains (efg1/efg1, efg1/efg1 cph1/cph1). Each Candida strain colonized the alimentary tract, infected keratinized gastric tissues to a similar extent, and induced a granulocyte-dominated inflammatory response in infected tissues. Both wild-type and mutant strains formed hyphae in vivo and were able to elicit an increase in cytokine [tumour necrosis factor alpha, interleukin (IL)-10 and IL-12] and chemokine (KC and macrophage inflammatory protein-2] mRNAs in infected tissues; however, administration of the wild-type strain was lethal for the Tgepsilon26 mice, whereas the mice colonized with the mutant strains survived. Death of the Tgepsilon26-colonized mice appeared to be due to occlusive oesophageal candidiasis, and not to disseminated candidiasis of endogenous origin. In contrast, the mutant strains exhibited a significantly reduced capacity to infect (frequency and severity) oro-oesophageal (tongue and oesophagus) tissues. Therefore, the two hyphal signalling-defective mutants were less able to infect oro-oesophageal tissues and were non-lethal, but retained their ability to colonize the alimentary tract with yeast and hyphae, infect keratinized gastric tissues, and evoke an inflammatory response in orogastric tissues.
Westwater
Caroline
C
Department of Stomatology, Medical University of South Carolina, Charleston, SC, USA.
Balish
Edward
E
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
Warner
Thomas F
TF
Department of Surgical Pathology, University of Wisconsin Medical School, Madison, WI, USA.
Nicholas
Peter J
PJ
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
Paulling
Emily E
EE
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
Schofield
David A
DA
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
D000818:Animals; D002176:Candida albicans / Q000235:genetics / Q000472:pathogenicity*; D002177:Candidiasis / Q000276:immunology*; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics; D041981:Gastrointestinal Tract / Q000382:microbiology / Q000473:pathology; D015870:Gene Expression; D005856:Germ-Free Life; D006098:Granulocytes / Q000276:immunology; D025301:Hyphae / Q000254:growth & development; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics; D014774:Virulence / Q000235:genetics*
C090837:CPH1 protein, Candida albicans; D018925:Chemokines; D016207:Cytokines; D004268:DNA-Binding Proteins; C121438:EFG1 protein, Candida albicans; D005656:Fungal Proteins; D014157:Transcription Factors