Distinct subsets of neutrophils crosstalk with cytokines and metabolites in patients with sepsis
Summary: Sepsis is a life-threatening condition caused by a dysregulated host response to infection. Despite continued efforts to understand the pathophysiology of sepsis, no effective therapies are currently available. While singular components of the aberrant immune response have been investigated...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-02-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223000251 |
| _version_ | 1828012398140719104 |
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| author | Upasana Parthasarathy Yi Kuang Gunjan Thakur John D. Hogan Thomas P. Wyche James E. Norton, Jr. Jason R. Killough Theodore R. Sana Caroline Beakes BaoJen Shyong Rena N. Zhang Dario A. Gutierrez Michael Filbin David C. Christiani Alex G. Therien Christopher H. Woelk Cory H. White Roberta Martinelli |
| author_facet | Upasana Parthasarathy Yi Kuang Gunjan Thakur John D. Hogan Thomas P. Wyche James E. Norton, Jr. Jason R. Killough Theodore R. Sana Caroline Beakes BaoJen Shyong Rena N. Zhang Dario A. Gutierrez Michael Filbin David C. Christiani Alex G. Therien Christopher H. Woelk Cory H. White Roberta Martinelli |
| author_sort | Upasana Parthasarathy |
| collection | DOAJ |
| description | Summary: Sepsis is a life-threatening condition caused by a dysregulated host response to infection. Despite continued efforts to understand the pathophysiology of sepsis, no effective therapies are currently available. While singular components of the aberrant immune response have been investigated, comprehensive studies linking different data layers are lacking. Using an integrated systems immunology approach, we evaluated neutrophil phenotypes and concomitant changes in cytokines and metabolites in patients with sepsis. Our findings identify differentially expressed mature and immature neutrophil subsets in patients with sepsis. These subsets correlate with various proteins, metabolites, and lipids, including pentraxin-3, angiopoietin-2, and lysophosphatidylcholines, in patients with sepsis. These results enabled the construction of a statistical model based on weighted multi-omics linear regression analysis for sepsis biomarker identification. These findings could help inform early patient stratification and treatment options, and facilitate further mechanistic studies targeting the trifecta of surface marker expression, cytokines, and metabolites. |
| first_indexed | 2024-04-10T09:32:13Z |
| format | Article |
| id | doaj.art-a7bebae0729f4859866504aea19e208c |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-10T09:32:13Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-a7bebae0729f4859866504aea19e208c2023-02-19T04:26:40ZengElsevieriScience2589-00422023-02-01262105948Distinct subsets of neutrophils crosstalk with cytokines and metabolites in patients with sepsisUpasana Parthasarathy0Yi Kuang1Gunjan Thakur2John D. Hogan3Thomas P. Wyche4James E. Norton, Jr.5Jason R. Killough6Theodore R. Sana7Caroline Beakes8BaoJen Shyong9Rena N. Zhang10Dario A. Gutierrez11Michael Filbin12David C. Christiani13Alex G. Therien14Christopher H. Woelk15Cory H. White16Roberta Martinelli17Discovery Immunology, Merck & Co.,Inc., Cambridge, MA, USADiscovery Immunology, Merck & Co.,Inc., Cambridge, MA, USAData and Genome Sciences, Merck & Co.,Inc., Cambridge, MA, USAData and Genome Sciences, Merck & Co.,Inc., Cambridge, MA, USAMass Spectrometry & Biophysics, Merck & Co.,Inc., Cambridge, MA, USAQuantitative Biosciences, Merck & Co.,Inc., West Point, PA, USADiscovery Immunology, Merck & Co.,Inc., Cambridge, MA, USAMass Spectrometry & Biophysics, Merck & Co.,Inc., Cambridge, MA, USAPulmonary and Critical Care Division, Massachusetts General Hospital, Boston, MA, USAPharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co.,Inc., West Point, PA, USAPharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co.,Inc., West Point, PA, USADiscovery Immunology, Merck & Co.,Inc., Cambridge, MA, USAPulmonary and Critical Care Division, Massachusetts General Hospital, Boston, MA, USAPulmonary and Critical Care Division, Massachusetts General Hospital, Boston, MA, USA; Department of Environmental Health and Epidemiology, Harvard School of Public Health, Boston, MA, USADiscovery Immunology, Merck & Co.,Inc., Cambridge, MA, USADiscovery Immunology, Merck & Co.,Inc., Cambridge, MA, USAData and Genome Sciences, Merck & Co.,Inc., Cambridge, MA, USA; Corresponding authorDiscovery Immunology, Merck & Co.,Inc., Cambridge, MA, USA; Corresponding authorSummary: Sepsis is a life-threatening condition caused by a dysregulated host response to infection. Despite continued efforts to understand the pathophysiology of sepsis, no effective therapies are currently available. While singular components of the aberrant immune response have been investigated, comprehensive studies linking different data layers are lacking. Using an integrated systems immunology approach, we evaluated neutrophil phenotypes and concomitant changes in cytokines and metabolites in patients with sepsis. Our findings identify differentially expressed mature and immature neutrophil subsets in patients with sepsis. These subsets correlate with various proteins, metabolites, and lipids, including pentraxin-3, angiopoietin-2, and lysophosphatidylcholines, in patients with sepsis. These results enabled the construction of a statistical model based on weighted multi-omics linear regression analysis for sepsis biomarker identification. These findings could help inform early patient stratification and treatment options, and facilitate further mechanistic studies targeting the trifecta of surface marker expression, cytokines, and metabolites.http://www.sciencedirect.com/science/article/pii/S2589004223000251ImmunityComponents of the immune systemCell biologySystems biology |
| spellingShingle | Upasana Parthasarathy Yi Kuang Gunjan Thakur John D. Hogan Thomas P. Wyche James E. Norton, Jr. Jason R. Killough Theodore R. Sana Caroline Beakes BaoJen Shyong Rena N. Zhang Dario A. Gutierrez Michael Filbin David C. Christiani Alex G. Therien Christopher H. Woelk Cory H. White Roberta Martinelli Distinct subsets of neutrophils crosstalk with cytokines and metabolites in patients with sepsis iScience Immunity Components of the immune system Cell biology Systems biology |
| title | Distinct subsets of neutrophils crosstalk with cytokines and metabolites in patients with sepsis |
| title_full | Distinct subsets of neutrophils crosstalk with cytokines and metabolites in patients with sepsis |
| title_fullStr | Distinct subsets of neutrophils crosstalk with cytokines and metabolites in patients with sepsis |
| title_full_unstemmed | Distinct subsets of neutrophils crosstalk with cytokines and metabolites in patients with sepsis |
| title_short | Distinct subsets of neutrophils crosstalk with cytokines and metabolites in patients with sepsis |
| title_sort | distinct subsets of neutrophils crosstalk with cytokines and metabolites in patients with sepsis |
| topic | Immunity Components of the immune system Cell biology Systems biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223000251 |
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