Phagolysosome

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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 microorganisms and pathogens. It takes place when the phagosome's and lysosome's membranes 'collide', at which point the lysosomal contents—including hydrolytic enzymes—are discharged into the phagosome in an explosive manner and digest the particles that the phagosome had ingested. Some products of the digestion are useful materials and are moved into the cytoplasm; others are exported by exocytosis.

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The process of phagocytosis showing phagolysosome formation. Lysosome(shown in green) fuses with phagosome to form a phagolysosome. Phagocytosis.svg
The process of phagocytosis showing phagolysosome formation. Lysosome(shown in green) fuses with phagosome to form a phagolysosome.

Membrane fusion of the phagosome and lysosome is regulated by the Rab5 protein, [1] a G protein that allows the exchange of material between these two organelles but prevents complete fusion of their membranes. [1]

When the phagosome and lysosome interact with one another, they form a fully developed phagolysosome. A fully developed phagolysosome consists of digestive and aseptic properties. The purpose of phagolysosomes is to act as a protective barrier. It is a defense line that kills pathogenic bacteria that may have slipped through detection of the other immune system cells. The extracellular space that surrounds the lysosome is very acidic which is important for degradation because most cells cannot handle an acidic environment and will die, with an exception of a few. [2]

For a phagolysosome to become a phagolysosome it must go through multiple steps. The first step is phagocytosis. Phagocytosis is when a cell engulfs an extracellular pathogen and entraps it in its membrane. When this happens the newly engulfed pathogen is called a phagosome. The next step is transportation and fusion. When it travels further into the cytosol, it comes into contact with the lysosome and fuses with it. The two fused membranes are now called phagolysosomes. The next step is digestion. Phagolysosome digests the pathogen revealing cell components (carbohydrates, lipids, and proteins). It will either be killed by apoptosis, engulfed by a macrophage, or presented to T-cells to induce an immune reaction. [3]

Function

Phagolysosomes function by reducing the pH of their internal environment, thus making them acidic. This serves as a defense mechanism against microbes and other harmful parasites and also provides a suitable medium for degradative enzyme activity. [4]

Microbes are destroyed within phagolysosomes by a combination of oxidative and non-oxidative processes. The oxidative process, also known as respiratory burst includes the "non-mitochondrial" production of reactive oxygen species. [5]

By lowering pH and concentrations of sources of carbon and nitrogen, phagolysomes inhibit growth of fungi. An example is the inhibition of hyphae in Candida albicans . [6]

In human neutrophils, the phagolysosomes destroy pathogens also by producing hypochlorous acid. [7]

Pathogens

Coxiella burnetii , the causative agent of Q fever, thrives and replicates in the acidic phagolysosomes of its host cell. [8] The acidity of the phagolysosome is essential for C.burnetii to transport glucose, glutamate, and proline, as well as for its synthesis of nucleic acids and proteins. [9]

Similarly, when in its amastigote stage, Leishmania obtains all its purine sources, various vitamins, and a number of its essential amino acids from the phagolysosome of its host. Leishmania also obtain heme from the proteolysis of proteins in the host phagolysosome . [10]

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References

  1. 1 2 Duclos S, Diez R, Garin J, Papadopoulou B, Descoteaux A, Stenmark H, et al. (October 2000). "Rab5 regulates the kiss and run fusion between phagosomes and endosomes and the acquisition of phagosome leishmanicidal properties in RAW 264.7 macrophages". Journal of Cell Science. 113 (19): 3531–3541. doi:10.1242/jcs.113.19.3531. PMID   10984443.
  2. ↑ Lee HJ, Woo Y, Hahn TW, Jung YM, Jung YJ (August 2020). "Formation and Maturation of the Phagosome: A Key Mechanism in Innate Immunity against Intracellular Bacterial Infection". Microorganisms. 8 (9): 1298. doi: 10.3390/microorganisms8091298 . PMC   7564318 . PMID   32854338.
  3. ↑ Nguyen JA, Yates RM (2021). "Better Together: Current Insights Into Phagosome-Lysosome Fusion". Frontiers in Immunology. 12: 636078. doi: 10.3389/fimmu.2021.636078 . PMC   7946854 . PMID   33717183.
  4. ↑ Levitz SM, Nong SH, Seetoo KF, Harrison TS, Speizer RA, Simons ER (February 1999). "Cryptococcus neoformans resides in an acidic phagolysosome of human macrophages". Infection and Immunity. 67 (2): 885–890. doi:10.1128/IAI.67.2.885-890.1999. PMC   96400 . PMID   9916104.
  5. ↑ Urban CF, Lourido S, Zychlinsky A (November 2006). "How do microbes evade neutrophil killing?". Cellular Microbiology. 8 (11): 1687–1696. doi:10.1111/j.1462-5822.2006.00792.x. PMID   16939535. S2CID   33708929.
  6. ↑ Erwig LP, Gow NA (March 2016). "Interactions of fungal pathogens with phagocytes". Nature Reviews. Microbiology. 14 (3): 163–176. doi:10.1038/nrmicro.2015.21. PMID   26853116. S2CID   19668359.
  7. ↑ Painter RG, Wang G (May 2006). "Direct measurement of free chloride concentrations in the phagolysosomes of human neutrophils". Analytical Chemistry. 78 (9): 3133–3137. doi:10.1021/ac0521706. PMID   16643004.
  8. ↑ Maurin M, Benoliel AM, Bongrand P, Raoult D (December 1992). "Phagolysosomes of Coxiella burnetii-infected cell lines maintain an acidic pH during persistent infection". Infection and Immunity. 60 (12): 5013–5016. doi:10.1128/iai.60.12.5013-5016.1992. PMC   258270 . PMID   1452331.
  9. ↑ Howe D, Mallavia LP (July 2000). "Coxiella burnetii exhibits morphological change and delays phagolysosomal fusion after internalization by J774A.1 cells". Infection and Immunity. 68 (7): 3815–3821. doi:10.1128/iai.68.7.3815-3821.2000. PMC   101653 . PMID   10858189.
  10. ↑ McConville MJ, de Souza D, Saunders E, Likic VA, Naderer T (August 2007). "Living in a phagolysosome; metabolism of Leishmania amastigotes". Trends in Parasitology. 23 (8): 368–375. doi:10.1016/j.pt.2007.06.009. PMID   17606406.
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