Abstract
Acute respiratory distress syndrome (ARDS) is the major cause of mortality among hospitalized acute lung injury (ALI) patients. Lung macrophages play an important role in maintaining the tissue-fluid homeostasis following injury. We recently showed that circulating monocytes recruited into the alveolar space suppressed the stimulator of type 1 interferon genes (STING) signaling in alveolar macrophages through sphingosine-1-phosphate (S1P). We used CD11b-DTR mice to deplete CD11b+ monocytes following LPS or Pseudomonas aeruginosa infection. Depletion of CD11b+ monocytes leads to the persistent inflammatory injury, infiltration of neutrophils, activation of STING signaling and mortality following lung infection. We demonstrated that adoptively transferred SPHK2-CD11b+ monocytes into CD11b-DTR mice after pathogenic infection rescue lung inflammatory injury.
Highlights
Acute lung injury (ALI) is associated with bacterial and viral infection such as Pseudomonas aeruginosa, SARSCOV2 virus, sepsis or drug toxicity which leads to acute respiratory distress syndrome (ARDS), predominantly in elderly patients
We showed that depletion of CD11b+Mφ transiently increased cGAMP generation in control lungs while causing persistent increase in cGAMP levels in Mφdep lungs, resulting in enhanced stimulator of type interferon genes (STING) signaling in these mice [7]
These findings indicate that recruited CD11b+Mφ in the airspace tightly control cGAMP-STING signaling in AMφ [7]
Summary
Acute lung injury (ALI) is associated with bacterial and viral infection such as Pseudomonas aeruginosa, SARSCOV2 virus, sepsis or drug toxicity which leads to acute respiratory distress syndrome (ARDS), predominantly in elderly patients. We showed that depletion of the recruited macrophage population, using diphtheria toxin (DT) in DTR-mice, during pathogenic insults induced proliferation and expansion of the inflammatory AMφ in the alveolar space [7]. We demonstrated that, during lung injury, CD11b+Mφ alter the alveolar niche to cause AMφ to become anti-inflammatory, J Cell Signal.
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