Stage specific assessment of Candida albicans phagocytosis by macrophages identifies cell wall composition and morphogenesis as key determinants.
Stage specific assessment of Candida albicans phagocytosis by macrophages identifies cell wall composition and morphogenesis as key determinants.
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DOI：
10.1371/journal.ppat.1002578
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发表时间：
2012
期刊：
影响因子：
6.7
通讯作者：
Erwig LP
中科院分区：
文献类型：
--
作者：
Lewis LE;Bain JM;Lowes C;Gillespie C;Rudkin FM;Gow NA;Erwig LP
白色念珠菌是一种主要的威胁人类生命的真菌病原体。宿主对系统性念珠菌感染的防御主要依赖于先天免疫系统细胞对真菌细胞的吞噬作用。在这项研究中，我们采用视频显微镜，加上先进的图像分析工具，以评估不同的C。白念珠菌细胞壁成分和酵母菌丝形态发生到巨噬细胞吞噬作用的特定阶段。我们发现巨噬细胞向C.白念珠菌的生长依赖于真菌细胞壁的糖基化状态，而不是细胞活力或从酵母到菌丝形式的形态发生转换。这不是最大巨噬细胞径迹速度差异的结果，而是源于更大百分比的巨噬细胞追求糖基化缺陷C。在吞噬作用测定的第一个小时期间，C.对于糖基化和酵母锁定形态发生突变株，附着于巨噬细胞表面的白色念珠菌显著延迟，但对于非存活细胞增强。菌丝细胞被吞噬的速度比酵母细胞慢，特别是那些菌丝超过20 µm的细胞，但是菌丝长度和低于这个阈值的吞噬速度之间没有相关性。结果表明，菌丝的空间定向性和菌丝是否为C。通过酵母或菌丝末端附着在巨噬细胞上的白色念珠菌也是吞噬速率的重要决定因素。将整个吞噬过程分解为各个组成部分，揭示了决定C。白色念珠菌被巨噬细胞吞噬。宿主对系统性念珠菌病的防御主要依赖于先天免疫系统的细胞，特别是中性粒细胞和巨噬细胞对真菌细胞的摄取和消除。在这里，我们使用活细胞视频显微镜结合先进的图像分析，以前所未有的细节对C。在两个不同的阶段（巨噬细胞迁移和结合的C. albicans的吞噬），白色念珠菌）的吞噬过程。本文介绍了研究C.白念珠菌可用于研究其他病原体和垂死宿主细胞的摄取。因此，我们的研究对更广泛的社区有直接的影响，并为未来研究其他吞噬细胞/微生物提供了蓝图，这将显着提高我们对有效吞噬作用机制的理解，并最终对感染的先天免疫反应。
Candida albicans is a major life-threatening human fungal pathogen. Host defence against systemic Candida infection relies mainly on phagocytosis of fungal cells by cells of the innate immune system. In this study, we have employed video microscopy, coupled with sophisticated image analysis tools, to assess the contribution of distinct C. albicans cell wall components and yeast-hypha morphogenesis to specific stages of phagocytosis by macrophages. We show that macrophage migration towards C. albicans was dependent on the glycosylation status of the fungal cell wall, but not cell viability or morphogenic switching from yeast to hyphal forms. This was not a consequence of differences in maximal macrophage track velocity, but stems from a greater percentage of macrophages pursuing glycosylation deficient C. albicans during the first hour of the phagocytosis assay. The rate of engulfment of C. albicans attached to the macrophage surface was significantly delayed for glycosylation and yeast-locked morphogenetic mutant strains, but enhanced for non-viable cells. Hyphal cells were engulfed at a slower rate than yeast cells, especially those with hyphae in excess of 20 µm, but there was no correlation between hyphal length and the rate of engulfment below this threshold. We show that spatial orientation of the hypha and whether hyphal C. albicans attached to the macrophage via the yeast or hyphal end were also important determinants of the rate of engulfment. Breaking down the overall phagocytic process into its individual components revealed novel insights into what determines the speed and effectiveness of C. albicans phagocytosis by macrophages. Host defence against systemic candidiasis relies mainly on the ingestion and elimination of fungal cells by cells of the innate immune system, especially neutrophils and macrophages. Here we have used live cell video microscopy coupled with sophisticated image analysis to generate a temporal and spatial analysis in unprecedented detail of the specific effects of C. albicans viability, cell wall composition, morphogenesis and spatial orientation on two distinct stages (macrophage migration and engulfment of bound C. albicans) of the phagocytosis process. The novel methods employed here to study phagocytosis of C. albicans could be applied to study other pathogens and uptake of dying host cells. Thus, our studies have direct implications for a much broader community and provide a blueprint for future studies with other phagocytes/microorganisms that would significantly enhance our understanding of the mechanisms that govern effective phagocytosis and ultimately the innate immune response to infection.
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DOI：
10.1073/pnas.95.13.7670
发表时间：
1998-06-23
影响因子：
11.1
作者：
Buurman, ET;Westwater, C;Gow, NAR
通讯作者：
Gow, NAR
影响因子：
64.5
作者：
Lo, HJ;Kohler, JR;Fink, GR
通讯作者：
Fink, GR
影响因子：
5.5
作者：
Cheng SC;van de Veerdonk FL;Lenardon M;Stoffels M;Plantinga T;Smeekens S;Rizzetto L;Mukaremera L;Preechasuth K;Cavalieri D;Kanneganti TD;van der Meer JW;Kullberg BJ;Joosten LA;Gow NA;Netea MG
通讯作者：
Netea MG
影响因子：
3.1
作者：
BISTONI, F;VECCHIARELLI, A;CASSONE, A
通讯作者：
CASSONE, A
影响因子：
6.4
作者：
Jouault, T;Fradin, C;Poulain, D
通讯作者：
Poulain, D