An integrated model of the recognition of Candida albicans by the innate immune system

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. IMPORTANCE Extensive work investigating fungal cell phagocytosis by macrophages and PMNs of the innate immune system has been carried out. These studies have been informative but have examined this phenomenon only when one phagocyte subset is present. The current study employed live-cell video microscopy to break down C. albicans phagocytosis into its component parts and examine the effect of a single phagocyte subset, versus a mixed phagocyte population, on these individual stages. Through this approach, we identified that the rate of fungal cell engulfment and rate of phagocyte killing altered significantly when both macrophages and PMNs were incubated in coculture with C. albicans compared to the rate of either phagocyte subset incubated alone with the fungus. This research highlights the significance of studying pathogen-host cell interactions with a combination of phagocytes in order to gain a greater understanding of the interactions that occur between cells of the host immune system in response to fungal invasion.

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In vivo effect of three fractions of Larrea divaricata Cav. (jarilla) on the innate immune system: macrophage response against Candida albicans

Mycoses ◽

10.1111/j.1439-0507.2010.02006.x ◽

2011 ◽

Vol 54 (6) ◽

pp. e718-e825 ◽

Cited By ~ 5

Author(s):

Renzo F. Martino ◽

Roberto C. Davicino ◽

María A. Mattar ◽

Yolanda A. Casali ◽

Silvia G. Correa ◽

...

Keyword(s):

Candida Albicans ◽

Immune System ◽

Innate Immune System ◽

Innate Immune ◽

Macrophage Response ◽

Larrea Divaricata

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Galanin Message-Associated Peptide Suppresses Growth and the Budded-to-Hyphal-Form Transition of Candida albicans

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00166-07 ◽

2007 ◽

Vol 51 (11) ◽

pp. 4167-4170 ◽

Cited By ~ 12

Author(s):

Isabella Rauch ◽

Linda Lundström ◽

Markus Hell ◽

Wolfgang Sperl ◽

Barbara Kofler

Keyword(s):

Candida Albicans ◽

Immune System ◽

Innate Immune System ◽

Human Keratinocytes ◽

Innate Immune ◽

Inhibiting Activity ◽

Growth Inhibiting

ABSTRACT The expression of the mRNA encoding galanin message-associated peptide (GMAP) in human keratinocytes is upregulated by lipopolysaccharides and exposure to Candida albicans. GMAP has growth-inhibiting activity against C. albicans and inhibits the budded-to-hyphal-form transition, establishing GMAP as a possible new component of the innate immune system.

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β-(1,3)-Glucan Unmasking in Some Candida albicans Mutants Correlates with Increases in Cell Wall Surface Roughness and Decreases in Cell Wall Elasticity

Infection and Immunity ◽

10.1128/iai.00601-16 ◽

2016 ◽

Vol 85 (1) ◽

Cited By ~ 18

Author(s):

Sahar Hasim ◽

David P. Allison ◽

Scott T. Retterer ◽

Alex Hopke ◽

Robert T. Wheeler ◽

...

Keyword(s):

Cell Wall ◽

Candida Albicans ◽

Immune System ◽

Innate Immune System ◽

Fungal Infections ◽

Innate Immune ◽

Surface Topology ◽

Wild Type ◽

Content Type ◽

Cell Wall Elasticity

ABSTRACT Candida albicans is among the most common human fungal pathogens, causing a broad range of infections, including life-threatening systemic infections. The cell wall of C. albicans is the interface between the fungus and the innate immune system. The cell wall is composed of an outer layer enriched in mannosylated glycoproteins (mannan) and an inner layer enriched in β-(1,3)-glucan and chitin. Detection of C. albicans by Dectin-1, a C-type signaling lectin specific for β-(1,3)-glucan, is important for the innate immune system to recognize systemic fungal infections. Increased exposure of β-(1,3)-glucan to the immune system occurs when the mannan layer is altered or removed in a process called unmasking. Nanoscale changes to the cell wall during unmasking were explored in live cells with atomic force microscopy (AFM). Two mutants, the cho1Δ/Δ and kre5Δ/Δ mutants, were selected as representatives that exhibit modest and strong unmasking, respectively. Comparisons of the cho1Δ/Δ and kre5Δ/Δ mutants to the wild type reveal morphological changes in their cell walls that correlate with decreases in cell wall elasticity. In addition, AFM tips functionalized with Dectin-1 revealed that the forces of binding of Dectin-1 to all of the strains were similar, but the frequency of binding was highest for the kre5Δ/Δ mutant, decreased for the cho1Δ/Δ mutant, and rare for the wild type. These data show that nanoscale changes in surface topology are correlated with increased Dectin-1 adhesion and decreased cell wall elasticity. AFM, using tips functionalized with immunologically relevant molecules, can map epitopes of the cell wall and increase our understanding of pathogen recognition by the immune system.

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