Plasma membrane abundance dictates phagocytic capacity and functional cross-talk in myeloid cells Journal Article
| Authors: | Winer, B. Y.; Settle, A. H.; Yakimov, A. M.; Jeronimo, C.; Lazarov, T.; Tipping, M.; Saoi, M.; Sawh, A.; Sepp, A. L. L.; Galiano, M.; Perry, J. S. A.; Wong, Y. Y.; Geissmann, F.; Cross, J.; Zhou, T.; Kam, L. C.; Pasolli, H. A.; Hohl, T.; Cyster, J. G.; Weiner, O. D.; Huse, M. |
| Article Title: | Plasma membrane abundance dictates phagocytic capacity and functional cross-talk in myeloid cells |
| Abstract: | Professional phagocytes like neutrophils and macrophages tightly control what they consume, how much they consume, and when they move after cargo uptake. We show that plasma membrane abundance is a key arbiter of these cellular behaviors. Neutrophils and macrophages lacking the G protein subunit Gβ4 exhibited profound plasma membrane expansion, accompanied by marked reduction in plasma membrane tension. These biophysical changes promoted the phagocytosis of bacteria, fungus, apoptotic corpses, and cancer cells. We also found that Gβ4-deficient neutrophils are defective in the normal inhibition of migration following cargo uptake. Sphingolipid synthesis played a central role in these phenotypes by driving plasma membrane accumulation in cells lacking Gβ4. In Gβ4 knockout mice, neutrophils not only exhibited enhanced phagocytosis of inhaled fungal conidia in the lung but also increased trafficking of engulfed pathogens to other organs. Together, these results reveal an unexpected, biophysical control mechanism central to myeloid functional decision-making. |
| Keywords: | mouse; animal; metabolism; animals; mice; mice, knockout; mice, inbred c57bl; c57bl mouse; immunology; neutrophil; cell membrane; neutrophils; bone marrow cell; macrophage; phagocytosis; macrophages; knockout mouse; myeloid cells |
| Journal Title: | Science Immunology |
| Volume: | 9 |
| Issue: | 96 |
| ISSN: | 2470-9468 |
| Publisher: | Amer Assoc Advancement Science |
| Date Published: | 2024-06-01 |
| Start Page: | eadl2388 |
| Language: | English |
| DOI: | 10.1126/sciimmunol.adl2388 |
| PUBMED: | 38848343 |
| PROVIDER: | scopus |
| PMCID: | PMC11485225 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF. Corresponding MSK authors are Benjamin Winer and Morgan Huse -- Source: Scopus |
