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Publication : Staphylococcus aureus stimulates neutrophil itaconate production that suppresses the oxidative burst.

First Author  Tomlinson KL Year  2023
Journal  Cell Rep Volume  42
Issue  2 Pages  112064
PubMed ID  36724077 Mgi Jnum  J:355005
Mgi Id  MGI:7438986 Doi  10.1016/j.celrep.2023.112064
Citation  Tomlinson KL, et al. (2023) Staphylococcus aureus stimulates neutrophil itaconate production that suppresses the oxidative burst. Cell Rep 42(2):112064
abstractText  Neutrophils are critical in the host defense against Staphylococcus aureus, a major human pathogen. However, even in the setting of a robust neutrophil response, S. aureus can evade immune clearance. Here, we demonstrate that S. aureus impairs neutrophil function by triggering the production of the anti-inflammatory metabolite itaconate. The enzyme that synthesizes itaconate, Irg1, is selectively expressed in neutrophils during S. aureus pneumonia. Itaconate inhibits neutrophil glycolysis and oxidative burst, which impairs survival and bacterial killing. In a murine pneumonia model, neutrophil Irg1 expression protects the lung from excessive inflammation but compromises bacterial clearance. S. aureus is thus able to evade the innate immune response by targeting neutrophil metabolism and inducing the production of the anti-inflammatory metabolite itaconate.
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