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Review
. 2021 Sep 22:2021:1601565.
doi: 10.1155/2021/1601565. eCollection 2021.

The Multiple Roles of Trogocytosis in Immunity, the Nervous System, and Development

Eileen Uribe-Querol  1 , Carlos Rosales  2
Affiliations
Review

The Multiple Roles of Trogocytosis in Immunity, the Nervous System, and Development

Eileen Uribe-Querol et al. Biomed Res Int. .

Abstract

Trogocytosis is a general biological process that involves one cell physically taking small parts of the membrane and other components from another cell. In trogocytosis, one cell seems to take little "bites" from another cell resulting in multiple outcomes from these cell-cell interactions. Trogocytosis was first described in protozoan parasites, which by taking pieces of host cells, kill them and cause tissue damage. Now, it is known that this process is also performed by cells of the immune system with important consequences such as cell communication and activation, elimination of microbial pathogens, and even control of cancer cells. More recently, trogocytosis has also been reported to occur in cells of the central nervous system and in various cells during development. Some of the molecules involved in phagocytosis also participate in trogocytosis. However, the molecular mechanisms that regulate trogocytosis are still a mystery. Elucidating these mechanisms is becoming a research area of much interest. For example, why neutrophils can engage trogocytosis to kill Trichomonas vaginalis parasites, but neutrophils use phagocytosis to eliminate already death parasites? Thus, trogocytosis is a significant process in normal physiology that multiple cells from different organisms use in various scenarios of health and disease. In this review, we present the basic principles known on the process of trogocytosis and discuss the importance in this process to host-pathogen interactions and to normal functions in the immune and nervous systems.

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Conflict of interest statement

The authors declare that there is no conflict of interest regarding the publication of this paper.

Figures

Figure 1
Figure 1
Examples of trogocytosis. (a) The “brain-eating” amoeba Naegleria fowleri can destroy neuron cells by taking (nibbling) little pieces off them. (b) The predatory slime mold Dictyostelium caveatum feeds upon other Dictyostelium species amoebas. (c) The intestinal parasitic amoeba Entamoeba histolytica actively nibbles pieces of live endothelial cells leading to cell lysis. (d) Immune cells use trogocytosis for cell communication. Antigens together with major histocompatibility complex (MHC) molecules can be transferred from antigen-presenting cells (APC) to T lymphocytes. After trogocytosis between immune cells, both cells continue alive. (e) Macrophages can perform trogocytosis to remove membrane antigens from antibody-coated cells. This form of trogocytosis has also been called antibody shaving. (f) Intracellular bacteria take advantage of trogocytosis to spread between cells. The bacteria Francisella tularensis infect and live within macrophages and can transfer from one cell to another through trogocytosis. In this process, the plasma membrane, cytoplasm, and live bacteria are transported from one infected macrophage to another.
Figure 2
Figure 2
Examples of trogocytosis to kill large cells. (a) Trichomonas vaginalis, a large and highly motile parasite, is attacked by neutrophils which surround and take “bites” of the parasite membrane until the parasite dies. (b) In vaginal tissues, the excess of sperm is eliminated by neutrophils. Since sperm cells are too large to be phagocytosed, neutrophils take “bites” of the sperm membrane and quickly reduced their motility and viability. (c) Macrophages can perform trogocytosis to kill antibody-coated tumor cells. (d) Astrocytes which are the central nervous system glial cells responsible for regulating synaptic neuronal networks take pieces of axon projections containing mitochondria from the optic nerve neurons through trogocytosis. (e) During development, Caenorhabditis elegans primordial germ cells connect to endodermal precursor cells in the interior of the embryo. These primordial cells form lobes that are removed and digested by endodermal cells through trogocytosis. This form of trogocytosis has also been called cell cannibalism.
Figure 3
Figure 3
Molecular mechanisms of trogocytosis in E. histolytica. The molecular mechanisms involved in trogocytosis are just beginning to be elucidated. (a) The amoeba Gal/GalNAc (galactose and N-acetyl-D-galactosamine) lectin binds to glycoproteins on intestinal endothelial cells. In the amoeba, the enzymes PI3K (phosphatidylinositol 3-kinase) and EhC2PK (amoebic C2-kinase) get activated. The main phosphoinositide present in the resting plasma membrane is phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], which serves as a substrate for PI3K to generate phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3]. Also, EhLTP1 (amoebic lipid transfer protein 1) (LTPs) is associated at the ligand attachment site at the initiation of trogocytosis. (b) PI(3,4,5)P3 is localized to the trogocytic cup as well as to the trogocytic tunnel. PI(3,4,5)P3 then recruits EhAGC kinases 1 (EhAGCK1) to the trogocytic cup, where it participates in regulating the formation of cytoskeletal structures that support the trogocytic tunnel. Also, PI(3,4,5)P3 recruits the FYVE domain-containing protein EhFP4 to the trogocytic tunnel. There, EhFP4 physically interacts with Rho/Rac small GTPases for controlling F-actin polymerization. Also, EhLTP3 (amoebic lipid transfer protein 3) is recruited onto the trogocytic tunnel at the intermediate stage of trogocytosis. (c) Also, phosphatidylinositol 3-phosphate (PI3P), another product of PI3K, accumulates to the distal end of the trogocytic cup. There, PI3P recruits EhSNX1 (amoebic sorting nexin SNX1), which specifically binds to Arp2/3 on the trogocytic tunnel to induce actin polymerization. (d) Finally, a trogosome is formed with a membrane enriched in PI3P, which also recruits EhSNX2 (amoebic sorting nexin SNX2). SNX1 on the trogosome membrane binds to the retromer component EhVps26, involved on transport of cysteine proteinases, which are also important for trogocytosis.
Figure 4
Figure 4
Molecular mechanisms of trogocytosis in immune cells. (a) T cell trogocytosis. T cell receptors (TCR) engage antigen (Ag) bound to major histocompatibility complex (MHC) molecules on the antigen-presenting cell (APC). In the T cell, the small GTPases RRas and RhoG, together with phosphatidylinositol 3-kinase (PI3K) and actin, participate in trogocytosis. Membrane proteins from the APC are transferred to the T cell. When the cells separate, both cells remain viable. (b) Neutrophils can kill tumor cells through trogocytosis. A tumor cell coated with antibodies (Ab) can be recognized by the neutrophil through its antibody Fc gamma receptors (FcγR). In the neutrophil, trogocytosis is activated by the participation of Syk (spleen tyrosine kinase), PI3K, and also actin. As a result of nibbling, the tumor cell gets killed.
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