期刊
TRAFFIC
卷 21, 期 8, 页码 522-533出版社
WILEY
DOI: 10.1111/tra.12752
关键词
endocytic capacity; endocytosis; heterogeneity; lysosome; M; tuberculosis; phagocytosis; phagosome maturation; tuberculosis
类别
资金
- Department of Science and Technology, Ministry of Science and Technology, Government of India [Max Planck partner group] Funding Source: Medline
- Max-Planck-Gesellschaft Funding Source: Medline
- National Centre for Biological Sciences [core funding] Funding Source: Medline
- Department of Biotechnology , Ministry of Science and Technology [Ramalingaswamy fellowship] Funding Source: Medline
Phagocytosis is a complex cellular uptake process involving multiple distinct steps of cargo recognition, uptake, phagosome maturation and eventual phagolysosome resolution. Emerging literature shows that heterogeneity of phagocytosis at multiple steps at a single cell level influences the population outcome. However, the determinants of phagocytic heterogeneity are not clear. Here we show that the variance in the endocytic capacity of individual cells in a macrophage population determines subsequent phagocytic uptake and trafficking. Our results document the extensive heterogeneity in the endocytic uptake of individual macrophages, and show that cells with higher endocytic capacity preferentially phagocytose diverse cargo, including pathogenicMycobacterium tuberculosis. Interestingly,M.tuberculosisinfected cells sustain the higher endocytic capacity following infection. Modulating endocytic capacity by inhibiting endocytosis reduces phagocytic uptake. Differential uptake ofM.tuberculosisinto cells with different endocytic capacities correlates with the efficiency of phagocytic delivery to lysosomes, thus contributing further to phagocytic as well as mycobacterial heterogeneity. Thus, variance in endocytic capacity is a determinant of generating heterogeneity in phagocytosis at multiple steps.
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