In vitro study of contact-mediated killing of Candida albicans hyphae by activated murine peritoneal macrophages in a serum-free medium

Abstract

Activated peritoneal macrophages obtained from Listeria-immune mice were demonstrated to kill nonphagocytosable Candida albicans hyphae by contact-mediated mechanisms in a serum-free synthetic medium. The actual killing of hyphae was confirmed by a microculture technique utilizing the dimorphic nature of the fungus. The most efficient candidacidal activity was demonstrated by the macrophages obtained from mice first immunized with live Listeria monocytogenes and then elicited with heat-killed L. monocytogenes cells. Resident macrophages from control mice showed only low candidacidal activity against C. albicans hyphae and yeast cells. Direct physical contact appeared to be required for macrophages to efficiently kill oversized C. albicans hyphae. Efficient in vitro killing of hyphae also required relatively high effector/target cell ratios (50 or higher). The contact-mediated candidacidal activity of activated macrophages was not significantly abrogated by oxygen-radical scavengers, suggesting the involvement of oxygen-independent mechanisms. These results suggest that the enhanced nonspecffic immunity to candidiasis seen in Listeria-immune hosts can be attributed, at least in part, to activated fungicidal macrophages. The ability of macrophages to detect and destroy both yeast and hyphal C. albicans cells is clearly an important element of the host defense against candidiasis.

Morphological and physiological changes induced by contact-dependent interaction between Candida albicans and Fusobacterium nucleatum

“…Due to a number of important physiological, structural, and biochemical differences, C. albicans yeast and hyphal forms often induce a differential host immune response 28 37 38 39 40 . The observed higher candidacidal activity of RAW cells against the hyphal form may be the result of contact-mediated killing of hyphae 41 as well as higher sensitivity of hyphae to nitrogen-containing compounds released by macrophages 42 . Our results suggest that interaction with F. nucleatum inhibits yeast-to-hyphae transition in C. albicans, thus retaining C. albicans in a more macrophage-resistant morphology.…”

Suppression of splenic macrophage Candida albicans phagocytosis following in vivo depletion of natural killer cells in immunocompetent BALB/c mice and T-cell-deficient nude mice

“…Thus, it is of great interest to dissect the innate mechanisms that operate in the resistance to systemic candidiasis. Results from in vitro assays [6] and from experimental animals [7] show that macrophages are important in the host defense against candidiasis, particularly during the early stages of infection. Macrophages are cells that can both modulate the development of a subsequent acquired immune response and also act as e¡ector cells to kill this fungus.…”

Suppression of splenic macrophageCandida albicansphagocytosis following in vivo depletion of natural killer cells in immunocompetent BALB/c mice and T-cell-deficient nude mice

“…Thus, it is of great interest to dissect the innate mechanisms that operate in the resistance to systemic candidiasis. Results from in vitro assays [6] and from experimental animals [7] show that macrophages are important in the host defense against candidiasis, particularly during the early stages of infection. Macrophages are cells that can both modulate the development of a subsequent acquired immune response and also act as effector cells to kill this fungus.…”