Neutrophil heterogeneity in complement C1q expression associated with sepsis mortality
Sepsis is a life-threatening systemic inflammatory condition causing approximately 11 million annual deaths worldwide. Although key hyperinflammation-based organ dysfunctions that drive disease pathology have been recognized, our understanding of the factors that predispose patients to septic mortal...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.965305/full |
| _version_ | 1818506169370542080 |
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| author | Alissa Trzeciak Raj Kumar Mongre Ma Rie Kim Kihong Lim Rafael A. Madero Christopher N. Parkhurst Anthony P. Pietropaoli Minsoo Kim |
| author_facet | Alissa Trzeciak Raj Kumar Mongre Ma Rie Kim Kihong Lim Rafael A. Madero Christopher N. Parkhurst Anthony P. Pietropaoli Minsoo Kim |
| author_sort | Alissa Trzeciak |
| collection | DOAJ |
| description | Sepsis is a life-threatening systemic inflammatory condition causing approximately 11 million annual deaths worldwide. Although key hyperinflammation-based organ dysfunctions that drive disease pathology have been recognized, our understanding of the factors that predispose patients to septic mortality is limited. Due to the lack of reliable prognostic measures, the development of appropriate clinical management that improves patient survival remains challenging. Here, we discovered that a subpopulation of CD49chigh neutrophils with dramatic upregulation of the complement component 1q (C1q) gene expression arises during severe sepsis. We further found that deceased septic patients failed to maintain C1q protein expression in their neutrophils, whereas septic survivors expressed higher levels of C1q. In mouse sepsis models, blocking C1q with neutralizing antibodies or conditionally knocking out C1q in neutrophils led to a significant increase in septic mortality. Apoptotic neutrophils release C1q to control their own clearance in critically injured organs during sepsis; thus, treatment of septic mice with C1q drastically increased survival. These results suggest that neutrophil C1q is a reliable prognostic biomarker of septic mortality and a potential novel therapeutic target for the treatment of sepsis. |
| first_indexed | 2024-12-10T22:00:52Z |
| format | Article |
| id | doaj.art-f4fc9b38ae7c4c05956a1183de6570d8 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T22:00:52Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f4fc9b38ae7c4c05956a1183de6570d82022-12-22T01:31:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.965305965305Neutrophil heterogeneity in complement C1q expression associated with sepsis mortalityAlissa Trzeciak0Raj Kumar Mongre1Ma Rie Kim2Kihong Lim3Rafael A. Madero4Christopher N. Parkhurst5Anthony P. Pietropaoli6Minsoo Kim7Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY, United StatesDepartment of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY, United StatesDepartment of Biomedical Engineering, University of Rochester Medical Center, Rochester, NY, United StatesDepartment of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY, United StatesDepartment of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY, United StatesDivision of Pulmonary and Critical Care Medicine, Weill-Cornell Medicine, New York, NY, United StatesPulmonary and Critical Care Medicine Division, University of Rochester, Rochester, NY, United StatesDepartment of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY, United StatesSepsis is a life-threatening systemic inflammatory condition causing approximately 11 million annual deaths worldwide. Although key hyperinflammation-based organ dysfunctions that drive disease pathology have been recognized, our understanding of the factors that predispose patients to septic mortality is limited. Due to the lack of reliable prognostic measures, the development of appropriate clinical management that improves patient survival remains challenging. Here, we discovered that a subpopulation of CD49chigh neutrophils with dramatic upregulation of the complement component 1q (C1q) gene expression arises during severe sepsis. We further found that deceased septic patients failed to maintain C1q protein expression in their neutrophils, whereas septic survivors expressed higher levels of C1q. In mouse sepsis models, blocking C1q with neutralizing antibodies or conditionally knocking out C1q in neutrophils led to a significant increase in septic mortality. Apoptotic neutrophils release C1q to control their own clearance in critically injured organs during sepsis; thus, treatment of septic mice with C1q drastically increased survival. These results suggest that neutrophil C1q is a reliable prognostic biomarker of septic mortality and a potential novel therapeutic target for the treatment of sepsis.https://www.frontiersin.org/articles/10.3389/fimmu.2022.965305/fullneutrophilsepsisefferocytosisC1qinflammation |
| spellingShingle | Alissa Trzeciak Raj Kumar Mongre Ma Rie Kim Kihong Lim Rafael A. Madero Christopher N. Parkhurst Anthony P. Pietropaoli Minsoo Kim Neutrophil heterogeneity in complement C1q expression associated with sepsis mortality Frontiers in Immunology neutrophil sepsis efferocytosis C1q inflammation |
| title | Neutrophil heterogeneity in complement C1q expression associated with sepsis mortality |
| title_full | Neutrophil heterogeneity in complement C1q expression associated with sepsis mortality |
| title_fullStr | Neutrophil heterogeneity in complement C1q expression associated with sepsis mortality |
| title_full_unstemmed | Neutrophil heterogeneity in complement C1q expression associated with sepsis mortality |
| title_short | Neutrophil heterogeneity in complement C1q expression associated with sepsis mortality |
| title_sort | neutrophil heterogeneity in complement c1q expression associated with sepsis mortality |
| topic | neutrophil sepsis efferocytosis C1q inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.965305/full |
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