Staphylococcus aureus stimulates neutrophil itaconate production that suppresses the oxidative burst
Summary: 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 productio...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-02-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112472300075X |
| _version_ | 1797936379548663808 |
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| author | Kira L. Tomlinson Sebastián A. Riquelme Swikrity Upadhyay Baskota Marija Drikic Ian R. Monk Timothy P. Stinear Ian A. Lewis Alice S. Prince |
| author_facet | Kira L. Tomlinson Sebastián A. Riquelme Swikrity Upadhyay Baskota Marija Drikic Ian R. Monk Timothy P. Stinear Ian A. Lewis Alice S. Prince |
| author_sort | Kira L. Tomlinson |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-04-10T18:29:56Z |
| format | Article |
| id | doaj.art-767b8e41e2d14568853587d3c6c14abe |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-10T18:29:56Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-767b8e41e2d14568853587d3c6c14abe2023-02-02T04:48:19ZengElsevierCell Reports2211-12472023-02-01422112064Staphylococcus aureus stimulates neutrophil itaconate production that suppresses the oxidative burstKira L. Tomlinson0Sebastián A. Riquelme1Swikrity Upadhyay Baskota2Marija Drikic3Ian R. Monk4Timothy P. Stinear5Ian A. Lewis6Alice S. Prince7Department of Pediatrics, Columbia University, New York, NY 10032, USADepartment of Pediatrics, Columbia University, New York, NY 10032, USADepartment of Pathology and Cell Biology, Columbia University, New York, NY 10032, USADepartment of Biological Sciences, University of Calgary, Calgary, AB T2N 1N4, CanadaDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, AustraliaDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, AustraliaDepartment of Biological Sciences, University of Calgary, Calgary, AB T2N 1N4, CanadaDepartment of Pediatrics, Columbia University, New York, NY 10032, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S221112472300075XCP: ImmunologyCP: Microbiology |
| spellingShingle | Kira L. Tomlinson Sebastián A. Riquelme Swikrity Upadhyay Baskota Marija Drikic Ian R. Monk Timothy P. Stinear Ian A. Lewis Alice S. Prince Staphylococcus aureus stimulates neutrophil itaconate production that suppresses the oxidative burst Cell Reports CP: Immunology CP: Microbiology |
| title | Staphylococcus aureus stimulates neutrophil itaconate production that suppresses the oxidative burst |
| title_full | Staphylococcus aureus stimulates neutrophil itaconate production that suppresses the oxidative burst |
| title_fullStr | Staphylococcus aureus stimulates neutrophil itaconate production that suppresses the oxidative burst |
| title_full_unstemmed | Staphylococcus aureus stimulates neutrophil itaconate production that suppresses the oxidative burst |
| title_short | Staphylococcus aureus stimulates neutrophil itaconate production that suppresses the oxidative burst |
| title_sort | staphylococcus aureus stimulates neutrophil itaconate production that suppresses the oxidative burst |
| topic | CP: Immunology CP: Microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S221112472300075X |
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