Inhibition of pseudohyphal growth as a neutrophil-mediated host defense mechanism against experimental deep Candida albicans infections in mice

Abstract

Neutrophils have recently been found to have microbistatic activity in addition to their well-described microbicidal mechanisms; therefore, a murine model of deep candidiasis was used to evaluate the possibility that both antimicrobial activities might participate in the host defense against this type of infection. In nonleukopenic animals, subcutaneous injection of Candida albicans yeast cells produced local abscesses and early metastatic spread of the infection to the kidneys. Although completely isolated within a dense neutrophilic infiltrate, a significant proportion of the fungal cells in the subcutaneous abscesses of these animals remained viable for at least 6 to 10 days after inoculation; the infections at this site were observed to resolve after spontaneous rupture of the abscesses. Growth of the organisms appeared to be suppressed at later time points in these animals, as evidenced by the markedly reduced proportions of multicelled pseudohyphae (representing organisms that had undergone cell division) observed in their abscess exudates as compared with those in samples from leukopenic animals. In addition, at 10 days after inoculation, very few multicelled pseudohyphae were observed histologically in the subcutaneous infections of nonleukopenic animals, whereas masses of these forms were found in leukopenic ones. Fluids from the abscesses of the nonleukopenic animals appeared to contain growth-inhibiting activity for C. albicans, in that the organisms could not grow in them unless additional zinc were to be added to the medium. This type of zinc-reversibility is a characteristic of neutrophil microbistatic activity.(ABSTRACT TRUNCATED AT 250 WORDS)