Cross-protection between A fumigatus and C albicans in mice is mediated by TH1 immunity. (A,C,E,G) Cross-protection by A fumigatus against gastrointestinal candidiasis. Mice treated with resting A fumigatus conidia intranasally a week before intragastric injection with Calbicans show reduced fungal growth (A), inflammatory cell recruitment (insets), and acanthosis compared with untreated animals (C). (B,D,F,H) Cross-protection by C albicans against invasive pulmonary aspergillosis. Mice treated with C albicans intragastrically a week before intranasal injection of resting A fumigatus conidia show reduced fungal growth (B) and inflammatory cell recruitment and amelioration of lung inflammatory pathology compared with untreated animals (D). (E-F) Infection with A fumigatus (E) or with C albicans (F) showed a significant increase in protective TH1 and regulatory T cells. (G-H) Cross-protection between A fumigatus and C albicans is dependent on IFN-γ. IFN-γ–deficient mice treated with A fumigatus (G) or C albicans (H) show no reduced fungal growth in the lungs or the stomach, respectively. The reduced fungal burden in IFN-γ–deficient mice is because of compensatory cytokines. Shown are fungal growth (CFUs/organ, mean ± SE), stomach (C) and lung histology (D), differential cell counts in cytospin preparations from stomachs (C) and lungs (D) and transcription factor mRNA expression in CD4+ T cells from mesenteric (candidiasis, E) or thoracic (aspergillosis, F) lymph nodes a week after infection. Shown are the results of one representative experiment of 3 independent experiments (for in vivo data) or pooled from 3 experiments (for in vitro assays). Bars represent SE. Photographs were taken using a high-resolution Olympus BX51 microscope, using Olympus Cell P 3.3 software. P, vaccinated versus unvaccinated animals.
