Heterogeneity in the endocytic capacity of individual macrophage in a population determines its subsequent phagocytosis, infectivity and subcellular trafficking.
|Title||Heterogeneity in the endocytic capacity of individual macrophage in a population determines its subsequent phagocytosis, infectivity and subcellular trafficking.|
|Publication Type||Journal Article|
|Year of Publication||2020|
|Authors||Sachdeva K, Goel M, Sundaramurthy V|
|Date Published||2020 Aug|
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 pathogenic Mycobacterium tuberculosis. Interestingly, M. tuberculosis infected cells sustain the higher endocytic capacity following infection. Modulating endocytic capacity by inhibiting endocytosis reduces phagocytic uptake. Differential uptake of M. tuberculosis into 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.
|Grant List||Ramalingaswamy fellowship / / Department of Biotechnology , Ministry of Science and Technology / |
Max Planck partner group / / Department of Science and Technology, Ministry of Science and Technology, Government of India /
/ / Max-Planck-Gesellschaft /
core funding / / National Centre for Biological Sciences /