Fig 1.
Survival curves after murine inhalative mucormycete infection.
Wild type mice (A,B), diabetic mice (C,D) or mice treated with cortisone acetate (E,F) or cyclophosphamide (G,H) were inhalatively infected with a low dosage of 6x106 (A,C,E,G) or a high dosage of 1.2x107 (B,D,F,H) spores of Lichtheimia corymbifera (LC) or Rhizopus arrhizus (RA). Survival was monitored for 14d post infection. The survival curves for the different fungi were compared using log-rank Mantel-Cox test; * p<0.05; ** p<0.01; *** p<0.005.
Fig 2.
Body weight and temperature as clinical parameters for mucormycete infection.
Wild type (wt) mice, diabetic mice or mice treated with cortisone acetate (CA) or cyclophosphamide (CP) were inhalatively infected with 6x106 (ld) or 1.2x107 (hd) spores of Lichtheimia corymbifera (LC) or Rhizopus arrhizus (RA). Body weight (A) and temperature (B) were controlled twice a day and are shown here for day 3 post infection. Body weight for the individual mice is calculated as % of body weight at day of infection. The different groups were statistically analyzed by one-way ANOVA; * p<0.05; ** p<0.01; *** p<0.005.
Fig 3.
Fungal load in lung tissue and blood.
Wild type (wt) mice, diabetic mice or mice treated with cortisone acetate (CA) or cyclophosphamide (CP) were inhalatively infected with 6x106 (low dose; ld) or 1.2x107 (high dose; hd) spores of Lichtheimia corymbifera (LC) or Rhizopus arrhizus (RA). (A) Fungal load in the lung was quantified by PCR at day of exitus. (B) Fungal dissemination was determined by CFU count in blood 24h post infection. The fungal load of the different groups was compared by one-way ANOVA; * p<0.05; ** p<0.01; *** p<0.005.
Fig 4.
Typical macroscopic and microscopic changes of Rhizopus arrhizus-infected lungs.
Wild-type mice, diabetic mice or mice treated with cortisone acetate or cyclophosphamide were inhalatively infected with 2x107 spores of Rhizopus arrhizus. Lungs were dissected and sections were stained with a combination of hematoxylin-eosin and methenamine silver staining. Top, left: macroscopic view of a lung from a cyclophosphamide-treated animal infected with R. arrhizus; top, right: fungal hyphae in the lung tissue; bottom, left: multinucleated giant cells and infiltrating lymphocytes; bottom right: transmural penetration of fungal hyphae into a lung blood vessel.
Fig 5.
Survival curves of mice inhalatively infected with mucormycetes under posaconazole prophylaxis.
Diabetic mice (A, B) or mice treated with cortisone acetate (C, D) or cyclophosphamide (E, F) were either mock-treated or treated with posaconazole. Inhalative infection with 2x107 spores of Lichtheimia corymbifera (LC) (A, C, E) or Rhizopus arrhizus (RA) (B, D, F) was performed 5d after start of drug application. Survival was monitored for 14d post infection. The survival curves for the different fungi were compared using log-rank Mantel-Cox test; * p<0.05; ** p<0.01; *** p<0.005.
Fig 6.
Survival, body weight and fungal load after mucormycete infection of mice with defined immunodeficiencies.
Wild type (wt) mice or mice lacking neutrophils (ΔNeu), complement factor C3 (ΔC3) or platelets (ΔPt), were inhalatively infected with 2x107 spores of Lichtheimia corymbifera (A, C, D) or Rhizopus arrhizus (B, C, D). (A, B) Survival was monitored for 14d post infection. (C) Body weight at time of death for the individual mice was calculated as percentage of body weight at day of infection. (D) Fungal load in the lung was quantified by PCR at day of exitus. * p<0.05; ** p<0.01; *** p<0.005.