Toxin-Induced Necroptosis Is a Major Mechanism of Lung Damage

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Staphylococcus aureus (SA) cause a highly inflammatory pneumonia associated with substantial morbidity and mortality. Much of this lung destruction is attributed to toxins that target specific receptors on human and murine cells. We demonstrate that the α-hemolysin (Hla) and other agr-regulated toxins activate RIP1/RIP3/MLKL-mediated necroptosis and IL-1β expression, through a mechanism that involves MLKL pore-formation and inflammasome activation. Cell death can be inhibited by osmoprotectants and K+ repletion. Necroptosis results in alveolar macrophage depletion and loss of anti-inflammatory signaling. Rip3-/- mice maintain significantly greater numbers of alveolar macrophages with anti-inflammatory phenotypes, CD206+ and CD200R+; decreased proinflammatory cytokine production; and improved SA clearance. Necroptosis represents a common mechanism of pulmonary damage activated by multiple SA toxins.

Vyšlo v časopise: Toxin-Induced Necroptosis Is a Major Mechanism of Lung Damage. PLoS Pathog 11(4): e32767. doi:10.1371/journal.ppat.1004820
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004820

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