NEUTROPHIL DEPLETION INCREASES SUSCEPTIBILITY TO SYSTEMIC AND VAGINALCANDIDIASIS IN MICE, AND REVEALS DIFFERENCES BETWEEN BRAIN AND KIDNEYIN MECHANISMS OF HOST-RESISTANCE

Infections caused by the yeast Candida albicans represent an increasin g threat to debilitated and immunosuppressed patients, and neutropenia is an important risk factor. Monoclonal antibody depletion of neutrop hils in mice was used to study the role of these cells in host resista nce. Ablation of neutrophils increased susceptibility to both systemic and vaginal challenge. The fungal burden in the kidney increased thre efold on day 1, and 100-fold on day 4, and infection was associated wi th extensive tissue destruction. However, a striking feature of the di sseminated disease in neutrophil-depleted animals was the altered patt ern of organ involvement. The brain, which is one of the primary targe t organs in normal mice, was little affected. There was a threefold in crease in the number of organisms recovered from the brains of neutrop hil-depleted mice on day 4 after infection, but detectable abscesses w ere rare. In contrast, the heart, which in normal mice shows only mino r lesions, developed severe tissue damage following neutrophil depleti on. Mice deficient in C5 demonstrated both qualitative and quantitativ e increases in the severity of infection after neutrophil depletion wh en compared with C5-sufficient strains. The results are interpreted as reflecting organ-specific differences in the mechanisms of host resis tance.