Staphylococcus aureus stimulates neutrophil itaconate production that suppresses the oxidative burst

• Published in: Cell reports (Cambridge) Vol. 42; no. 2; p. 112064
• Main Authors: Tomlinson, Kira L., Riquelme, Sebastián A., Baskota, Swikrity Upadhyay, Drikic, Marija, Monk, Ian R., Stinear, Timothy P., Lewis, Ian A., Prince, Alice S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.02.2023; Elsevier
• Subjects: CP: Immunology; CP: Microbiology; itaconate; NADPH oxidase; neutrophils; oxidative burst; pathogenesis; pneumonia; Staphylococcus aureus; CP: Immunology; pathogenesis; oxidative burst; itaconate; pneumonia; NADPH oxidase; CP: Microbiology; neutrophils; Staphylococcus aureus
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.112064

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. [Display omitted] •Itaconate limits bacterial clearance during S. aureus pneumonia•Neutrophils are the main source of itaconate during S. aureus infection•Itaconate impairs neutrophil survival by inhibiting glycolysis•Itaconate impedes neutrophil bacterial killing by inhibiting the oxidative burst Staphylococcus aureus is a major human pathogen that causes persistent lung infections. Tomlinson et al. demonstrate that S. aureus elicits a specific metabolic response from neutrophils—the primary immune cells required for eliminating S. aureus—that impairs their ability to kill the bacteria and clear the infection.