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Pathogen destruction versus intracellular survival: the role of lipids as phagosomal fate determinants
Benjamin E. Steinberg, Sergio Grinstein
Benjamin E. Steinberg, Sergio Grinstein
Published June 2, 2008
Citation Information: J Clin Invest. 2008;118(6):2002-2011. https://doi.org/10.1172/JCI35433.
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Science in Medicine

Pathogen destruction versus intracellular survival: the role of lipids as phagosomal fate determinants

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Abstract

Phagocytosis is a key component of the innate immune response and of the clearance of apoptotic bodies. Phagosome formation and subsequent maturation require extensive cytoskeletal rearrangement and precisely choreographed vesicular fusion and fission events. The objectives of this review are to highlight the functional importance of lipids in the phagocytic process, to discuss how pathogenic microorganisms can in some cases manipulate host lipid metabolism to either co-opt or disrupt phagosome maturation and promote their own survival, and to describe how defective phagosomal lipid metabolism can result in disease.

Authors

Benjamin E. Steinberg, Sergio Grinstein

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Figure 4

Intracellular bacteria co-opt or disrupt phagosomal lipid metabolism as a survival strategy.

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Intracellular bacteria co-opt or disrupt phagosomal lipid metabolism as ...
M. tuberculosis secretes the glycosylated PI analog lipoarabinomannan (LAM) to inhibit the production of PI(3)P by Vps34 in addition to secreting the phosphatase SapM, which dephosphorylates PI(3)P. Together, these effectors decrease vacuolar PI(3)P to arrest phagosome maturation and produce a favorable intracellular niche for M. tuberculosis survival. S. enterica injects the effector SigD into the cell. This phosphatase depletes PI(4,5)P2 from the plasma membrane, leading to bacterial invasion into the host cell. Once inside, SigD has been suggested to dephosphorylate PI(3,4,5)P3 to produce PI(3)P. Alternatively, SigD products might modulate Vps34 in order to increase vacuolar PI(3)P. These effects help the bacterium divert the maturation of the invasion vacuole away from the conventional antimicrobial trajectory of phagosomes.

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