Phagocytosis is the mechanism of capture and degradation of pathogens or debris that is performed by professional cells of the immune system. In certain circumstances, this process is impaired, which can lead to the development of opportunistic pathogens or chronic inflammation. We study the mechanims of capture and degradation of phagocytic cells, their impact on immune responses and their alterations by viral infections such as the Human Immunodeficiency Virus (HIV-1).
Professional phagocytes are specialized cells of the immune system that play a major role in innate and adaptive immune responses. Phagocytosis and degradation of invading microorganisms or debris is crucial for bacterial clearance and resolution of inflammation. In addition, presentation of antigens and cytokine secretion, which are late events determined by the pathway of internalization, are key elements of the immune responses. Therefore, it is crucial to understand the mechanisms of phagocytosis, especially of cell debris or microorganisms.
Our goal is to dissect the mechanisms used by phagocytes and in particular the coordinated activities of signaling pathways, membrane trafficking and cytoskeleton dynamics and their effect on the outcome of immune responses. We also analyze precisely the mechanisms that allow pathogen development in HIV-infected macrophages. Finally, we recently showed that part of the internalized material can be regurgitated without degradation and captured by B lymphocytes, a process that we aim to characterize further to better understand and manipulate the humoral immune response.
Marie-Anaïs F, Mazzolini J, Herit F and Niedergang F. Dynamin-actin cross-talk contributes to phagosome formation and closure. Traffic (2016) 17 : 487-499.
Niedergang F, Di Bartolo V, Alcover A. Comparative Anatomy of Phagocytic and Immunological Synapses. Front Immunol. (2016) Jan 28;7:18. Review.
Niedergang F., Phagocytosis. In: Ralph A Bradshaw and Philip D Stahl (Editors-in-Chief), Encyclopedia of Cell Biology, Vol 2, Waltham, MA: Academic Press, 2016, pp. 751-757.
Dumas A, Lê‑Bury G, Marie‑Anaïs F, Herit F, Mazzolini J, Guilbert T, Bourdoncle P., Russell DG, Benichou S, Zahraoui A, and Niedergang F. The HIV-1 protein Vpr impairs phagosome maturation by controlling microtubule-dependent trafficking.
J. Cell Biol. (2015) 211 : 359-372
Deschamps C, Echard E and Niedergang F. Phagocytosis and cytokinesis: do cells use common tools to cut and to eat ? HIghlights on common themes and differences. Traffic (2013) 4: 355-364. Review.
Marion S., Mazzolini J., Herit F., Bourdoncle P., Kambou-Pene N., Hailfinger S., Sachse M., Benmerah A., Echard A., Thome M. and Niedergang F. The NF-κB signaling protein Bcl10 regulates actin dynamics by controlling AP1 and OCRL-bearing vesicles. Dev Cell (2012) 23 : 954-967.