![Phagocytosis2](https://upload.wikimedia.org/wikipedia/commons/e/e6/Phagocytosis2.png)
In
cell biology, a phagosome is a
vesicle
Vesicle may refer to:
; In cellular biology or chemistry
* Vesicle (biology and chemistry)
In cell biology, a vesicle is a structure within or outside a cell, consisting of liquid or cytoplasm enclosed by a lipid bilayer. Vesicles form nat ...
formed around a particle engulfed by a
phagocyte
Phagocytes are cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek ', "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek ...
via
phagocytosis
Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is ...
. Professional phagocytes include
macrophages
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...
,
neutrophils, and
dendritic cells
Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. The ...
(DCs).
A phagosome is formed by the fusion of the
cell membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
around a
microorganism
A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...
, a
senescent cell or an
apoptotic cell. Phagosomes have
membrane-bound proteins to recruit and fuse with
lysosomes
A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane prote ...
to form mature
phagolysosomes
In biology, a phagolysosome, or endolysosome, is a cytoplasmic body formed by the fusion of a phagosome with a lysosome in a process that occurs during phagocytosis. Formation of phagolysosomes is essential for the intracellular destruction of micr ...
. The lysosomes contain
hydrolytic enzymes and
reactive oxygen species
In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen.
The reduction of molecular oxygen () p ...
(ROS) which kill and digest the
pathogens
In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a ger ...
. Phagosomes can also form in non-professional phagocytes, but they can only engulf a smaller range of particles, and do not contain ROS. The useful materials (e.g.
amino acids) from the digested particles are moved into the
cytosol
The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...
, and waste is removed by
exocytosis. Phagosome formation is crucial for tissue homeostasis and both innate and adaptive host defense against pathogens.
However, some
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few micrometr ...
can exploit phagocytosis as an invasion strategy. They either reproduce inside of the phagolysosome ''(''e.g. ''
Coxiella'' spp.) or escape into the
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...
before the phagosome fuses with the lysosome (e.g. ''
Rickettsia
''Rickettsia'' is a genus of nonmotile, gram-negative, nonspore-forming, highly pleomorphic bacteria that may occur in the forms of cocci (0.1 μm in diameter), bacilli (1–4 μm long), or threads (up to about 10 μm long). The term "ricke ...
'' spp.). Many Mycobacteria, including ''
Mycobacterium tuberculosis'' and ''
Mycobacterium avium paratuberculosis
''Mycobacterium avium'' subspecies ''paratuberculosis'' (MAP) is an obligate pathogenic bacterium in the genus '' Mycobacterium''. It is often abbreviated ''M. paratuberculosis'' or ''M. avium'' ssp. ''paratuberculosis''. It is the causative ag ...
'', can manipulate the host
macrophage to prevent lysosomes from fusing with phagosomes and creating mature phagolysosomes. Such incomplete maturation of the phagosome maintains an environment favorable to the pathogens inside it.
Formation
Phagosomes are large enough to degrade whole bacteria, or
apoptotic
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes incl ...
and senescent cells, which are usually >0.5μm in diameter.
This means a phagosome is several orders of magnitude bigger than an
endosome
Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can ...
, which is measured in
nanometres
330px, Different lengths as in respect to the molecular scale.
The nanometre (international spelling as used by the International Bureau of Weights and Measures; SI symbol: nm) or nanometer (American and British English spelling differences#-re ...
.
Phagosomes are formed when pathogens or
opsonins
Opsonins are extracellular proteins that, when bound to substances or cells, induce phagocytes to phagocytose the substances or cells with the opsonins bound. Thus, opsonins act as tags to label things in the body that should be phagocytosed (i.e. ...
bind to a transmembrane receptor, which are randomly distributed on the phagocyte cell surface. Upon binding, "outside-in" signalling triggers
actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ov ...
polymerisation and
pseudopodia formation, which surrounds and fuses behind the microorganism.
Protein kinase C,
phosphoinositide 3-kinase, and
phospholipase C (PLC) are all needed for signalling and controlling particle internalisation.
More cell surface receptors can bind to the particle in a zipper-like mechanism as the pathogen is surrounded, increasing the binding
avidity In biochemistry, avidity refers to the accumulated strength of ''multiple'' affinities of individual non-covalent binding interactions, such as between a protein receptor and its ligand, and is commonly referred to as functional affinity. Avidity di ...
.
Fc receptor (FcR),
complement receptors
A complement receptor is a membrane-bound receptor belonging to the complement system, which is part of the innate immune system. Complement receptors bind effector protein fragments that are produced in response to antigen-antibody complexes or ...
(CR),
mannose receptor
The mannose receptor (Cluster of Differentiation 206, CD206) is a C-type lectin primarily present on the surface of macrophages, immature dendritic cells and liver sinusoidal endothelial cells, but is also expressed on the surface of skin cells ...
and
dectin-1 are phagocytic receptors, which means that they can induce phagocytosis if they are expressed in non-phagocytic cells such as
fibroblasts
A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells ...
.
Other proteins such as
Toll-like receptors
Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single-pass membrane-spanning receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize s ...
are involved in pathogen pattern recognition and are often recruited to phagosomes but do not specifically trigger phagocytosis in non-phagocytic cells, so they are not considered phagocytic receptors.
Opsonisation
Opsonins are molecular tags such as
antibodies and
complements that attach to pathogens and up-regulate phagocytosis.
Immunoglobulin G (IgG) is the major type of antibody present in the
serum. It is part of the
adaptive immune system
The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system ...
, but it links to the
innate response by recruiting macrophages to phagocytose pathogens. The antibody binds to microbes with the variable
Fab domain, and the
Fc domain
The fragment crystallizable region (Fc region) is the tail region of an antibody that interacts with cell surface receptors called Fc receptors and some proteins of the complement system. This property allows antibodies to activate the immune ...
binds to Fc receptors (FcR) to induce phagocytosis.
Complement-mediated internalisation has much less significant membrane protrusions, but the downstream signalling of both pathways converge to activate
Rho GTPases
Rho GTPase may refer to:
*Any member of the Rho family of GTPases
*The members of the Rho family of GTPases belonging to the '' Rho subclass''
*RHOA
Transforming protein RhoA, also known as Ras homolog family member A (RhoA), is a small GTPase ...
.
They control actin polymerisation which is required for the phagosome to fuse with endosomes and lysosomes.
Non-phagocytic cells
Other non-professional phagocytes have some degree of phagocytic activity, such as thyroid and bladder epithelial cells that can engulf erythrocytes and retinal epithelial cells that internalise retinal rods.
However non-professional phagocytes do not express specific phagocytic receptors such as FcR and have a much lower rate of internalisation.
Some invasive bacteria can also induce phagocytosis in non-phagocytic cells to mediate host uptake. For example, ''
Shigella
''Shigella'' is a genus of bacteria that is Gram-negative, facultative anaerobic, non-spore-forming, nonmotile, rod-shaped, and genetically closely related to '' E. coli''. The genus is named after Kiyoshi Shiga, who first discovered it in 1 ...
'' can secrete toxins that alter the host cytoskeleton and enter the basolateral side of
enterocytes
Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells which line the inner surface of the small and large intestines. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase it ...
.
Structure
As the membrane of the phagosome is formed by the fusion of the plasma membrane, the basic composition of the
phospholipid bilayer
The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many vir ...
is the same. Endosomes and lysosomes then fuse with the phagosome to contribute to the membrane, especially when the engulfed particle is very big, such as a
parasite
Parasitism is a close relationship between species, where one organism, the parasite, lives on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The entomologist E. O. Wilson has ...
.
They also deliver various membrane proteins to the phagosome and modify the organelle structure.
Phagosomes can engulf artificial low-density
latex
Latex is an emulsion (stable dispersion) of polymer microparticles in water. Latexes are found in nature, but synthetic latexes are common as well.
In nature, latex is found as a milky fluid found in 10% of all flowering plants (angiosperms ...
beads and then purified along a
sucrose concentration gradient, allowing the structure and composition to be studied.
By purifying phagosomes at different time points, the maturation process can also be characterised. Early phagosomes are characterised by Rab5, which transition into Rab7 as the vesicle matures into late phagosomes.
Maturation process
The nascent phagosome is not inherently bactericidal. As it matures, it becomes more acidic from pH 6.5 to pH 4, and gains characteristic protein markers and hydrolytic enzymes. The different enzymes function at various optimal pH, forming a range so they each work in narrow stages of the maturation process. Enzyme activity can be fine-tuned by modifying the pH level, allowing for greater flexibility. The phagosome moves along
microtubules
Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 a ...
of the
cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is com ...
, fusing with endosomes and lysosomes sequentially in a dynamic
"kiss-and-run" manner.
This intracellular transport depends on the size of the phagosomes. Larger organelles (with a diameter of about 3 μm) are transported very persistently from the cell periphery towards the perinuclear region whereas smaller organelles (with a diameter of about 1 μm) are transported more bidirectionally back and forth between cell center and cell periphery.
Vacuolar proton pumps (v-ATPase) are delivered to the phagosome to acidify the organelle compartment, creating a more hostile environment for pathogens and facilitating protein degradation. The bacterial proteins are denatured in low pH and become more accessible to the proteases, which are unaffected by the acidic environment. The enzymes are later recycled from the phagolysosome before egestion so they are not wasted. The composition of the phospholipid membrane also changes as the phagosome matures.
Fusion may take minutes to hours depending on the contents of the phagosome; FcR or mannose receptor-mediated fusion last less than 30 minutes, but phagosomes containing latex beads may take several hours to fuse with lysosomes.
It is suggested that the composition of the phagosome membrane affects the rate of maturation. ''Mycobacterium tuberculosis'' has a very hydrophobic
cell wall, which is hypothesised to prevent membrane recycling and recruitment of fusion factors, so the phagosome does not fuse with lysosomes and the bacterium avoids degradation.
Smaller lumenal molecules are transferred by fusion faster than larger molecules, which suggests that a small aqueous channel forms between the phagosome and other vesicles during "kiss-and-run", through which only limited exchange is allowed.
Fusion regulation
Shortly after internalisation, F-actin depolymerises from the newly formed phagosome so it becomes accessible to endosomes for fusion and delivery of proteins.
The maturation process is divided into early and late stages depending on characteristic protein markers, regulated by small Rab GTPases. Rab5 is present on early phagosomes, and controls the transition to late phagosomes marked by Rab7.
Rab5 recruits PI-3 kinase and other tethering proteins such as Vps34 to the phagosome membrane, so endosomes can deliver proteins to the phagosome. Rab5 is partially involved in the transition to Rab7, via the CORVET complex and the HOPS complex in yeast.
The exact maturation pathway in mammals is not well understood, but it is suggested that HOPS can bind Rab7 and displace the
guanosine nucleotide dissociation inhibitor
In molecular biology, the Guanosine dissociation inhibitors (GDIs) constitute a protein family, family of small GTPases that serve a regulatory role in vesicle (biology), vesicular membrane traffic. GDIs bind to the GDP-bound form of Rho and Rab s ...
(GDI).
Rab11 is involved in membrane recycling.
Phagolysosome
The phagosome fuses with lysosomes to form a phagolysosome, which has various bactericidal properties. The phagolysosome contains reactive oxygen and
nitrogen species (ROS and RNS) and hydrolytic enzymes. The compartment is also acidic due to proton pumps (v-ATPases) that transport H
+ across the membrane, used to denature the bacterial proteins.
The exact properties of phagolysosomes vary depending on the type of phagocyte. Those in dendritic cells have weaker bactericidal properties than those in macrophages and neutrophils. Also, macrophages are divided into pro-inflammatory "killer" M1 and "repair" M2. The phagolysosomes of M1 can metabolise
arginine into highly reactive
nitric oxide, while M2 use arginine to produce
ornithine
Ornithine is a non-proteinogenic amino acid that plays a role in the urea cycle. Ornithine is abnormally accumulated in the body in ornithine transcarbamylase deficiency. The radical is ornithyl.
Role in urea cycle
L-Ornithine is one of the produ ...
to promote cell proliferation and tissue repair.
Function
Pathogen degradation
Macrophages and neutrophils are professional phagocytes in charge of most of the pathogen degradation, but they have different bactericidal methods. Neutrophils have granules that fuse with the phagosome. The granules contain
NADPH oxidase
NADPH oxidase (nicotinamide adenine dinucleotide phosphate oxidase) is a membrane-bound enzyme complex that faces the extracellular space. It can be found in the plasma membrane as well as in the membranes of phagosomes used by neutrophil white ...
and
myeloperoxidase
Myeloperoxidase (MPO) is a peroxidase enzyme that in humans is encoded by the ''MPO'' gene on chromosome 17. MPO is most abundantly expressed in neutrophil granulocytes (a subtype of white blood cells), and produces hypohalous acids to carry ...
, which produce toxic oxygen and chlorine derivatives to kill pathogens in an
oxidative burst
Respiratory burst (or oxidative burst) is the rapid release of the reactive oxygen species (ROS), superoxide anion () and hydrogen peroxide (), from different cell types.
This is usually utilised for mammalian immunological defence, but also pla ...
. Proteases and
anti-microbial peptides are also released into the phagolysosome. Macrophages lack granules, and rely more on phagolysosome acidification,
glycosidases
Glycoside hydrolases (also called glycosidases or glycosyl hydrolases) catalyze
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the rea ...
, and proteases to digest microbes.
Phagosomes in dendritic cells are less acidic and have much weaker hydrolytic activity, due to a lower concentration of lysosomal proteases and even the presence of protease inhibitors.
Inflammation
Phagosome formation is tied to
inflammation
Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
via common signalling molecules. PI-3 kinase and PLC are involved in both the internalisation mechanism and triggering inflammation.
The two proteins, along with Rho GTPases, are important components of the innate immune response, inducing
cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
production and activating the
MAP kinase signalling cascade. Pro-inflammatory cytokines including
IL-1β
Interleukin-1 beta (IL-1β) also known as leukocytic pyrogen, leukocytic endogenous mediator, mononuclear cell factor, lymphocyte activating factor and other names, is a cytokine protein that in humans is encoded by the ''IL1B'' gene."Catabolin" ...
,
IL-6,
TNFα, and
IL-12 are all produced.
The process is tightly regulated and the inflammatory response varies depending on the particle type within the phagosome. Pathogen-infected apoptotic cells will trigger inflammation, but damaged cells that are degraded as part of the normal tissue turnover do not. The response also differs according to the opsonin-mediated phagocytosis. FcR and mannose receptor-mediated reactions produce pro-inflammatory reactive oxygen species and
arachidonic acid molecules, but CR-mediated reactions do not result in those products.
Antigen presentation
Immature dendritic cells (DCs) can phagocytose, but mature DCs cannot due to changes in Rho GTPases involved in cytoskeleton remodelling.
The phagosomes of DCs are less hydrolytic and acidic than those of macrophages and neutrophils, as DCs are mainly involved in
antigen presentation
Antigen presentation is a vital immune process that is essential for T cell immune response triggering. Because T cells recognize only fragmented antigens displayed on cell surfaces, antigen processing must occur before the antigen fragment, n ...
rather than pathogen degradation. They need to retain protein fragments of a suitable size for specific bacterial recognition, so the peptides are only partially degraded.
Peptides from the bacteria are trafficked to the
Major Histocompatibility Complex (MHC). The peptide antigens are presented to
lymphocytes, where they bind to
T-cell receptors and activates
T-cells
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
, bridging the gap between innate and adaptive immunity.
This is specific to
mammals
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur o ...
,
birds, and jawed fish, as
insects
Insects (from Latin ') are pancrustacean hexapod invertebrates of the class Insecta. They are the largest group within the arthropod phylum. Insects have a chitinous exoskeleton, a three-part body (head, thorax and abdomen), three pairs of j ...
do not have adaptive immunity.
Nutrient
Ancient single-celled organisms such as
amoeba
An amoeba (; less commonly spelled ameba or amœba; plural ''am(o)ebas'' or ''am(o)ebae'' ), often called an amoeboid, is a type of cell or unicellular organism with the ability to alter its shape, primarily by extending and retracting pseudop ...
use phagocytosis as a way to acquire nutrients, rather than an immune strategy. They engulf other smaller microbes and digest them within the phagosome of around one bacterium per minute, which is much faster than professional phagocytes.
For the soil amoeba ''
Dictyostelium discoideum
''Dictyostelium discoideum'' is a species of soil-dwelling amoeba belonging to the phylum Amoebozoa, infraphylum Mycetozoa. Commonly referred to as slime mold, ''D. discoideum'' is a eukaryote that transitions from a collection of unicellular ...
'', their main food source is the bacteria ''
Legionella pneumophila'', which causes
Legionnaire's disease in humans.
Phagosome maturation in amoeba is very similar to that in macrophages, so they are used as a model organism to study the process.
Tissue clearance
Phagosomes degrade senescent cells and apoptotic cells to maintain tissue homeostasis.
Erythrocytes
Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
have one of the highest turnover rates in the body, and they are phagocytosed by macrophages in the
liver
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
and
spleen
The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes . . In the
embryo, the process of removing dead cells is not well-characterised, but it is not performed by macrophages or other cells derived from
hematopoietic stem cells
Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the very first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within ...
.
It is only in the adult that apoptotic cells are phagocytosed by professional phagocytes. Inflammation is only triggered by certain
pathogen- or
damage-associated molecular patterns (PAMPs or DAMPs), the removal of senescent cells is non-inflammatory.
Autophagosome
Autophagosomes are different from phagosomes in that they are mainly used to selectively degrade damaged cytosolic organelles such as
mitochondria (
mitophagy Mitophagy is the selective degradation of mitochondria by autophagy. It often occurs to defective mitochondria following damage or stress. The process of mitophagy was first described over a hundred years ago by Margaret Reed Lewis and Warren Harmo ...
). However, when the cell is starved or stressed, autophagosomes can also non-selectively degrade organelles to provide the cell with amino acids and other nutrients.
Autophagy is not limited to professional phagocytes, it is first discovered in rat
hepatocytes
A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass.
These cells are involved in:
* Protein synthesis
* Protein storage
* Transformation of carbohydrates
* Synthesis of cholesterol, ...
by cell biologist
Christian de Duve
Christian René Marie Joseph, Viscount de Duve (2 October 1917 – 4 May 2013) was a Nobel Prize-winning Belgian cytologist and biochemist. He made serendipitous discoveries of two cell organelles, peroxisome and lysosome, for which he shared ...
. Autophagosomes have a double membrane, the inner one from the engulfed organelle, and the outer membrane is speculated to be formed from the
endoplasmic reticulum or the
ER-Golgi Intermediate Compartment (ERGIC).
The autophagosome also fuses with lysosomes to degrade its contents. When ''M. tuberculosis'' inhibit phagosome acidification,
Interferon gamma
Interferon gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheeloc ...
can induce autophagy and rescue the maturation process.
Bacterial evasion and manipulation
Many bacteria have evolved to evade the bactericidal properties of phagosomes or even exploit phagocytosis as an invasion strategy.
*''Mycobacterium tuberculosis'' target M2 macrophages at the lower parts of the respiratory pathway, which do not produce ROS. ''M. tuberculosis'' can also manipulate the signalling pathways by secreting phosphatases such as PtpA and SapM, which disrupt protein recruitment and block phagosome acidification.
*''Legionella pneumophila'' can re-model the phagosome membrane to imitate vesicles in other parts of the secretory pathway, so lysosomes do not recognise the phagosome and do not fuse with it. The bacterium secretes toxins that interfere with host trafficking, so the ''Legionella''-containing vacuole recruits membrane proteins usually found on the endoplasmic reticulum or the ERGIC.
This re-directs secretory vesicles to the modified phagosome and deliver nutrients to the bacterium.
*''
Listeria monocytogenes
''Listeria monocytogenes'' is the species of pathogenic bacteria that causes the infection listeriosis. It is a facultative anaerobic bacterium, capable of surviving in the presence or absence of oxygen. It can grow and reproduce inside the host ...
'' secretes a pore-forming protein
listeriolysin O
Listeriolysin O (LLO) is a hemolysin produced by the bacterium ''Listeria monocytogenes'', the pathogen responsible for causing listeriosis. The toxin may be considered a virulence factor, since it is crucial for the virulence of ''L. monocytogenes ...
so the bacterium can escape the phagosome into the cytosol. Listeriolysin is activated by the acidic environment of the phagosome.
In addition, ''Listeria'' secrete two phospholipase C enzymes that facilitate in phagosome escape.
See also
*
Autophagosome
An autophagosome is a spherical structure with double layer membranes. It is the key structure in macroautophagy, the intracellular degradation system for cytoplasmic contents (e.g., abnormal intracellular proteins, excess or damaged organelles, i ...
*
Phagocyte
Phagocytes are cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek ', "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek ...
References
{{Organelles
Cell biology
Vesicles