Phagolysosome

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

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.

The lysosome, containing hydrolytic enzymes digests the ingested particles in the phagosome when the phagosome migrates to the cytoplasm during phagocytosis. Membrane fusion of the phagosome and lysosome is regulated by Rab 5 protein.[1] This G Protein allows the exchange of material between these two organelles but prevents complete fusion of their membranes.[1] Formation of phagolysosomes are essential for the intracellular destruction of microorganisms and pathogens and requires an increase in intracellular calcium ion concentration.[2] Reactive oxygen species and reactive nitrogen species are produced in the nutrient-limiting environment of phagolysosomes.[3] Research studies show that phagolysosomes may contain more carbon sources and nutrients than other organelles in the endo-lysosomal pathway.[4]

When the membranes of the phagosome and lysosome 'collide',the lysosomal contents are discharged in an explosive manner and toxic molecules are released into the phagosome.Products of the digestion are either moved into the cytoplasm (useful materials) or exported by exocytosis.

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.[5]

The Q fever causative agent,Coxiella burnetii thrives and replicates in the acidic phagolysosomes of its host cell.[6] The acidity of the phagolysosome is essential for C.burnetii to transport glucose,glutamate,proline and also for the synthesis of nucleic acids and proteins.[7]

Importance

Phagolysosome formation is important for the destruction of microbes and parasites.Microbes are destroyed by a combination of oxidative and non-oxidative processes in phagolysosomes.The oxidative process also known as respiratory burst includes the "non-mitochondrial" production of reactive oxygen species.[8]

Phagolysomes inhibit fungal growth due to high cation concentration and low carbon and nitrogen sources .A typical example is the inhbition of Candida albicans filamentation.[9]

Leishmania amastigotes obtain all their purine sources,various vitamins and a number of essential amino acids from the phagolysosome of its host.Uptake of these substances is facilitated by proton symporters.Leishmania also obtain amino acids and heme from the proteolysis of proteins in the host phagolysosome and exogenous proteins are transported to the phagolysosome by autophagy and endocytosis.[10]

Human neutrophils also produce hypochlorous acid to destroy pathogens in phagolysosmes.[11]

References

  1. 1 2 Duclos, S.; Diez, R.; Garin, J.; Papadopoulou, B.; Descoteaux, A.; Stenmark, H.; Desjardins, M. (2000-10-01). "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 Pt 19: 3531–3541. ISSN 0021-9533. PMID 10984443.
  2. ↑ "Phagosome-lysosome fusion is a calcium-independent event in macrophages". The Journal of Cell Biology. 132 (1): 49–61. 1996-01-01. ISSN 0021-9525. PMC 2120694Freely accessible. PMID 8567729.
  3. ↑ Slauch, James M. (2016-11-20). "How does the oxidative burst of macrophages kill bacteria? Still an open question". Molecular microbiology. 80 (3): 580–583. doi:10.1111/j.1365-2958.2011.07612.x. ISSN 0950-382X. PMC 3109634Freely accessible. PMID 21375590.
  4. ↑ McConville, Malcolm J.; Saunders, Eleanor C.; Kloehn, Joachim; Dagley, Michael J. (2015-01-01). "Leishmania carbon metabolism in the macrophage phagolysosome- feast or famine?". F1000Research. 4 (F1000 Faculty Rev): 938. doi:10.12688/f1000research.6724.1. PMC 4648189Freely accessible. PMID 26594352.
  5. ↑ Levitz, S. M.; Nong, S. H.; Seetoo, K. F.; Harrison, T. S.; Speizer, R. A.; Simons, E. R. (1999-02-01). "Cryptococcus neoformans resides in an acidic phagolysosome of human macrophages". Infection and Immunity. 67 (2): 885–890. ISSN 0019-9567. PMC 96400Freely accessible. PMID 9916104.
  6. ↑ Maurin, M.; Benoliel, A. M.; Bongrand, P.; Raoult, D. (1992-12-01). "Phagolysosomes of Coxiella burnetii-infected cell lines maintain an acidic pH during persistent infection". Infection and Immunity. 60 (12): 5013–5016. ISSN 0019-9567. PMC 258270Freely accessible. PMID 1452331.
  7. ↑ Howe, Dale; Mallavia, Louis P. (2016-11-19). "Coxiella burnetii Exhibits Morphological Change and Delays Phagolysosomal Fusion after Internalization by J774A.1 Cells". Infection and Immunity. 68 (7): 3815–3821. ISSN 0019-9567. PMC 101653Freely accessible. PMID 10858189.
  8. ↑ Urban, Constantin F.; Lourido, Sebastian; Zychlinsky, Arturo (2006-11-01). "How do microbes evade neutrophil killing?". Cellular Microbiology. 8 (11): 1687–1696. doi:10.1111/j.1462-5822.2006.00792.x. ISSN 1462-5814. PMID 16939535.
  9. ↑ Erwig, Lars P.; Gow, Neil A. R. (2016-03-01). "Interactions of fungal pathogens with phagocytes". Nature Reviews. Microbiology. 14 (3): 163–176. doi:10.1038/nrmicro.2015.21. ISSN 1740-1534. PMID 26853116.
  10. ↑ "Living in a phagolysosome; metabolism of Leishmania amastigotes". www.sciencedirect.com. Retrieved 2016-11-20.
  11. ↑ Painter, Richard G.; Wang, Guoshun (2006-05-01). "Direct measurement of free chloride concentrations in the phagolysosomes of human neutrophils". Analytical Chemistry. 78 (9): 3133–3137. doi:10.1021/ac0521706. ISSN 0003-2700. PMID 16643004.
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