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    The phagocytosis

    What is this?

    A short history

    Elie MetchnikoffIt has been 100 years since the death of Elie Metchnikoff and we take this opportunity to revisit the topic of phagocytosis. After much scientific controversy between proponents of cellular versus humoral immunity, these two aspects of immunology were eventually awarded the Nobel Prize for Medicine in 1908, with the award going to both Elie Metchnikoff and Paul Ehrlich. Elie Metchnikoff (Ukrainian) was the first scientist to study phagocytosis in detail and this predated understanding its importance in immunity. The discovery of phagocytosis was made while holidaying in Sicily with his family, where he found that starfish larvae were able to swallow rose thorns.

     

    Video on humoral and cellular immunity: click on the image

     

    What is phagocytosis?

    Phagocytic cell internalizing Salmonella Typhimurium

    This is the mechanism by which cells can ingest material, pathogens, cells or cell debris. It is important in homeostasis, development, cell renewal and the immune response during the acute phase of inflammation where it serves to provide the first line of defence. Sentinel resident cell or cells recruited to sites of inflammation or infection can eliminate "dangerous" agents during the initial phase and this process also participate in clearing dead cells during the later stages of the inflammatory response.

     

     

     

     

    What are the phagocytic cells?

    We can distinguish between "professional" phagocytic cells such as macrophages, neutrophils and dendritic cells, which act as sentinels of the immune system and represent the first line of defence versus other cells which possess phagocytic capabilities. For example, epithelial cells within the retina can effectively control photoreceptors damaged by light. Phagocytes therefore include both immune cells and cells involved in general homeostasis.

    What are the tools used to study phagocytosis?

    Macrophage being phagocytose red blood cells (high density), electron microscopy picture at transmissionMany approaches have been used to examine phagocytosis including microscopy on fixed or living cells, fluorescence microscopy to observe the process of phagocytosis in cell culture, total internal reflection fluorescence microscopy which provides information on the resolution or closing of phagosomes and electron microscopy to give very accurate details on compartments or the phagocytosis of virus or small particles.

     

     

     

     

     

     

    Teams from the Cochin Institute working directly on phagocytosis

    Macrophage being phagocytose red blood cells (stained green), scanning electron microscopy picturedMacrophage infected with HIV-1 after the phagocytosis of targets (blue), which are transported to the compartments for degradation (yellow)The team lead by Florence Niedergang aims to determine the mechanisms which allow phagocytic cells to engulf particles, debris, or other pathogens and to provide a clear understanding of the subcellular mechanisms involved, which can differ depending on the target. Furthermore, this group studies the defects in phagocytic cells which can occur during infection such as HIV, or in chronic inflammatory situations. HIV infection results in a decrease in phagocytic functions and in turn allows opportunistic infections to occur. As they are interested in the human disease, this team uses primary macrophages derived from blood precursors and co-infects them with HIV-1 and bacteria such as particular strains of Salmonella including Salmonella Typhimurium, which has evolved alongside the virus in Africa.

     

    Numerous neutrophils (circular polylobed nuclei) and macrophages (large cells with round nuclei) in bronchial fluid in mice after injecting a bacteria component, lipopolysaccharideThe team lead by Véronique Witko-Sarsat is interested in neutrophils, which represent over 60% of circulating leukocytes and are a key in defence against bacteria. Neutrophils contain oxidants, antibiotic proteins and highly microbicidal proteases which facilitate bacterial killing and are also endowed with an important pro-inflammatory potential. There are a number of serious genetic diseases where neutrophils exhibit defects in migration or function (for example septic CGD) and prior to the era of antibodies, these diseases were fatal during infancy. Other pathologies this lab is interested involve the persistence of neutrophils at the site of inflammation or infection which are deleterious, such as vasculitis (inflammation of blood vessels), cystic fibrosis (lung inflammation) or rheumatoid arthritis. Oxidants and proteases required for the destruction of bacteria can also be extremely toxic to the tissue when the inflammation is not resolved effectively. This team focuses on understanding the mechanisms responsible for neutrophil survival and subsequent clearance by macrophages at the site of inflammation.   Controlling these mechanisms could open the door for new anti-inflammatory therapeutic avenues.

     

     

     Teams also work on phagocytosis:

    - The team lead by Clotilde Randriamampita and Emmanuel Donnadieu study the role of macrophages in tumour immune cell infiltrates

    - The team lead by Anne Hosmalin studies the phagocytosis of living cells by dendritic cells and the role of this in activating  the immune system the link to immunitaire

    - The Erythropoiesis and regulators' group lead by Patrick Mayeux and Didier Bouscary studying erythrophagocytosis during differentiation of blood cells rouges

     

    Finally, other teams conducting research on the area of phagocytosis

    include studying how pathogens hijack cells (epithelial, endothelial) and force their internalisation:  teams Cécile Arrieumerlou, Gordon Langsley, Lavazec Catherine, Claire Poyart and Agnes Fouet, Clarisse Berlioz-Torrent and Stéphane Emiliani, and Morgane Bomsel.

    Last April, Florence Niedergang and Véronique Witko-Sarsat organized a workshop dedicated to phagocytes, the "Phagocyte Workshop" at the 50th Congress of the ESCI (Congress of the European Society of Clinical Investigation).

    On 26 September, the Pasteur Institute paid tribute to Elie Metchnikoff at the symposium "From Embryology to Aging, from phagocytes to Microbiota" backed by an exhibition on the life and scientific work of this famous Pasteur alumni. www.metchnikofflegacy2016.org/

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