Phosphoinositol 3-phosphate acts as a timer for reactive oxygen species production in the phagosome.

Production of reactive oxygen species in the phagosome by the NADPH oxidase is critical for mammalian immune defense against microbial infections and phosphoinositides are important regulators in this process. Phosphoinositol 3-phosphate (PI(3)P) regulates production at the phagosome via p40^phox by an unknown mechanism. This study tested the hypothesis that PI(3)P controls duanyu1670 production by regulating the presence of p40^phox and p67^phox at the phagosomal membrane. Pharmacologic inhibition of PI(3)P synthesis at the phagosome decreased the duanyu1670 production both in differentiated PLB-985 cells and human neutrophils. It also releases p67^phox, the key cytosolic subunit of the oxidase, and p40^phox from the phagosome. The knockdown of the PI(3)P phosphatase MTM1 or Rubicon or both increases the level of PI(3)P at the phagosome. That increase enhances duanyu1670 production inside the phagosome and triggers an extended accumulation of p67^phox at the phagosome. Furthermore, the overexpression of MTM1 at the phagosomal membrane induces the disappearance of PI(3)P from the phagosome and prevents sustained duanyu1670 production. In conclusion, PI(3)P, indeed, regulates duanyu1670 production by maintaining p40^phox and p67^phox at the phagosomal membrane.

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