Augmented inhibition of growth of Candida albicans by neutrophils in the presence of lactoferrin

Abstract

The combined inhibitory effects of neutrophils and lactoferrins on the growth of Candida albicans were examined. Murine or human neutrophils partially inhibited growth of C. albicans when cultured with C. albicans in vitro. The growth inhibition was augmented by a combination of neutrophils and more than 30 microg/ml of bovine lactoferrin or 1 microg/ml of human lactoferrin, concentrations less than 1/10-1/200 their inhibiting concentrations when used alone. The inhibition of C. albicans was also enhanced by combination of neutrophils and bovine apolactoferrin or iron-bound holo-lactoferrin, but not by transferrin. Combination effects of neutrophils and lactoferrin were also observed in a condition where there was no contact between neutrophils and Candida cells. These results suggest that neutrophils inhibit the growth of C. albicans regardless of whether there is direct contact between them and Candida cells: neutrophil growth inhibition effects were augmented in the presence of a physiological concentration of lactoferrin, perhaps through some action of lactoferrin other than chelation of ferric ion.

The Early Transcriptional Response of Human Granulocytes to Infection withCandida albicansIs Not Essential for Killing but Reflects Cellular Communications

“…Numerous studies in the past have examined aspects of the neutrophil-pathogen response, investigating various microorganisms, including C. albicans (8,23,29,32,35). Recent studies have also investigated the global transcriptional responses of C. albicans to phagocytes/neutrophils, monocytes, and macrophages (10,21,33).…”

“…Components potentially involved in killing include lactoferrin, which is secreted in the PMN fractions. Several previous studies have demonstrated the candidacidal properties of lactoferrin (29,39,41). The only gene representing the neutrophil granule proteins, which was significantly upregulated, was the protease urokinase-type plasminogen activator (i.e., PLAU) (13).…”

Regulation ofCandida albicansMorphogenesis by Fatty Acid Metabolites

“…albicans germ tube assay. A crystal violet-based germ tube assay was used to measure germination as previously described (1,31,46). C. albicans strain CHN1 was grown in sabouraud dextrose broth (SDB) at 22°C (room temperature) while shaking for 48 to 72 h. Samples were washed in 1ϫ phosphatebuffered saline (PBS) and resuspended in 100% fetal bovine serum (FBS) to give a final concentration of 10 6 yeast cells/ml.…”

Candida albicans, Cryptococcus neoformans or Aspergillus fumigatus Induces an Antifungal Activity in Mouse Serum, which is Different from Transferrin

“…Transferrin [8,23], lactoferrin [1,7,16] and calprotectin [1,19,24] are well known antifungal substances associated with innate immunity in humans and animals. Transferrin and lactoferrin, which are present in blood and in mucus secretions, respectively, are chelating proteins sequestering iron while calprotecitn, which is present in neutrophil, is a chelating protein for calcium and zinc.…”