Altered Dynamics of Candida albicans Phagocytosis by Macrophages and PMNs When Both Phagocyte Subsets Are Present

Abstract

An important first line of defense against Candida albicans infections is the killing of fungal cells by professional phagocytes of the innate immune system, such as polymorphonuclear cells (PMNs) and macrophages. In this study, we employed live-cell video microscopy coupled with dynamic image analysis tools to provide insights into the complexity of C. albicans phagocytosis when macrophages and PMNs were incubated with C. albicans alone and when both phagocyte subsets were present. When C. albicans cells were incubated with only one phagocyte subtype, PMNs had a lower overall phagocytic capacity than macrophages, despite engulfing fungal cells at a higher rate once fungal cells were bound to the phagocyte surface. PMNs were more susceptible to C. albicans-mediated killing than macrophages, irrespective of the number of C. albicans cells ingested. In contrast, when both phagocyte subsets were studied in coculture, the two cell types phagocytosed and cleared C. albicans at equal rates and were equally susceptible to killing by the fungus. The increase in macrophage susceptibility to C. albicans-mediated killing was a consequence of macrophages taking up a higher proportion of hyphal cells under these conditions. In the presence of both PMNs and macrophages, C. albicans yeast cells were predominantly cleared by PMNs, which migrated at a greater speed toward fungal cells and engulfed bound cells more rapidly. These observations demonstrate that the phagocytosis of fungal pathogens depends on, and is modified by, the specific phagocyte subsets present at the site of infection.

Candida albicans Quorum Sensing Molecules Stimulate Mouse Macrophage Migration

“…This difference is intriguing because engulfed white cells are able to survive within and then escape from macrophages in vitro (16)(17)(18). This in vitro result is compatible with the importance of macrophages in vivo for the early elimination of C. albicans (19,20) because macrophages which have engulfed C. albicans secrete immunoregulatory cytokines including interleukin-6 (IL-6), IL-1␤, IL-10, and tumor necrosis factor alpha (TNF-␣) (21) prior to the escape of C. albicans. These cytokines presumably promote the development and chemotactic migration of other innate immune cells, including neutrophils, which are more capable of killing C. albicans (22).…”

“…White-cell supernatants of C. albicans, but not opaque-cell supernatants, stimulate chemotaxis of neutrophils (14). Since macrophages interact differently with opaque cells compared to white cells (15,20), we hypothesized that, like neutrophils, macrophages might display differential migration patterns toward white and opaque C. albicans. We first sought to determine whether C. albicans white-cell supernatants preferentially stimulate macrophage migration relative to the opaque-cell supernatants as assayed by a transwell cell migration (Fig.…”

Innate immune cell response uponCandida albicansinfection

“…Co-culture of PMNs and macrophages showed that macrophages had higher ability of engulfing hyphae while PMNs played a predominant role in clearing yeast form C. albicans. 89 But when they were incubated separately, PMNs showed lower overall phagocytic capacity but higher susceptibility as compared with macrophages. 89 Taken together, it is hard to judge which phagocyte is more efficient for the lack of researches especially in vivo.…”

“…89 But when they were incubated separately, PMNs showed lower overall phagocytic capacity but higher susceptibility as compared with macrophages. 89 Taken together, it is hard to judge which phagocyte is more efficient for the lack of researches especially in vivo. New evidence also reveals that human macrophages may take up apoptotic neutrophils, so that they can own the antimicrobial peptides or acquire neutrophil granules to promote their antimicrobial activity.…”

“…89,90 TLR2, TLR4 and dectin-1 are all participating in the recognition of C. albicans and the highly expressed CR3 (complement receptor 3) and FcgR assist in the process of opsonization. 91 Investigations have clearly shown that several proinflammatory cytokines facilitate the migration of PMNs to the site of infection, such as IL-6, 92 IL-8 93 IL-17 94 and TNF-a.…”