The monocyte-derived cytokine response in whole blood from preterm newborns against sepsis-related bacteria is similar to term newborns and adults
IntroductionSepsis is characterized by a dysregulated innate immune response. It is a leading cause of morbidity and mortality in newborns, in particular for newborns that are born premature. Although previous literature indicate that the pro-inflammatory response may be impaired in preterm newborns...
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1353039/full |
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| author | Jop Jans Sven C. J. van Dun Renske Gorissen Roel F. A. Pieterman Tess S. Voskamp Sam Schoenmakers Hendrik Robert Taal Wendy W. J. Unger |
| author_facet | Jop Jans Sven C. J. van Dun Renske Gorissen Roel F. A. Pieterman Tess S. Voskamp Sam Schoenmakers Hendrik Robert Taal Wendy W. J. Unger |
| author_sort | Jop Jans |
| collection | DOAJ |
| description | IntroductionSepsis is characterized by a dysregulated innate immune response. It is a leading cause of morbidity and mortality in newborns, in particular for newborns that are born premature. Although previous literature indicate that the pro-inflammatory response may be impaired in preterm newborns, serum levels of monocyte-derived cytokines, such as TNF-α and IL-6, vary highly between newborns and can reach adult-like concentrations during sepsis. These contradictory observations and the severe consequences of neonatal sepsis in preterm newborns highlight the need for a better understanding of the pro-inflammatory cytokine response of preterm newborns to improve sepsis-related outcomes.Methods and resultsUsing an in vitro model with multiple read outs at the transcriptional and protein level, we consistently showed that the monocyte-derived cytokine response induced by sepsis-related bacteria is comparable between preterm newborns, term newborns and adults. We substantiated these findings by employing recombinant Toll-like receptor (TLR) ligands and showed that the activation of specific immune pathways, including the expression of TLRs, is also similar between preterm newborns, term newborns and adults. Importantly, we showed that at birth the production of TNF-α and IL-6 is highly variable between individuals and independent of gestational age.DiscussionThese findings indicate that preterm newborns are equally capable of mounting a pro-inflammatory response against a broad range of bacterial pathogens that is comparable to term newborns and adults. Our results provide a better understanding of the pro-inflammatory response by preterm newborns and could guide the development of interventions that specifically modulate the pro-inflammatory response during sepsis in preterm newborns. |
| first_indexed | 2024-04-24T22:56:47Z |
| format | Article |
| id | doaj.art-27391a2550fd43268911229e6d3399cf |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-24T22:56:47Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-27391a2550fd43268911229e6d3399cf2024-03-18T04:41:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13530391353039The monocyte-derived cytokine response in whole blood from preterm newborns against sepsis-related bacteria is similar to term newborns and adultsJop Jans0Sven C. J. van Dun1Renske Gorissen2Roel F. A. Pieterman3Tess S. Voskamp4Sam Schoenmakers5Hendrik Robert Taal6Wendy W. J. Unger7Laboratory of Pediatrics, Department of Pediatrics, University Medical Center Rotterdam, Erasmus Medical Center - Sophia, Rotterdam, NetherlandsLaboratory of Pediatrics, Department of Pediatrics, University Medical Center Rotterdam, Erasmus Medical Center - Sophia, Rotterdam, NetherlandsLaboratory of Pediatrics, Department of Pediatrics, University Medical Center Rotterdam, Erasmus Medical Center - Sophia, Rotterdam, NetherlandsLaboratory of Pediatrics, Department of Pediatrics, University Medical Center Rotterdam, Erasmus Medical Center - Sophia, Rotterdam, NetherlandsLaboratory of Pediatrics, Department of Pediatrics, University Medical Center Rotterdam, Erasmus Medical Center - Sophia, Rotterdam, NetherlandsDepartment of Obstetrics and Gynaecology, Erasmus Medical Center, Rotterdam, NetherlandsDepartment of Neonatal and Paediatric Intensive Care, Division of Neonatology, Erasmus University Medical Center, Rotterdam, NetherlandsLaboratory of Pediatrics, Department of Pediatrics, University Medical Center Rotterdam, Erasmus Medical Center - Sophia, Rotterdam, NetherlandsIntroductionSepsis is characterized by a dysregulated innate immune response. It is a leading cause of morbidity and mortality in newborns, in particular for newborns that are born premature. Although previous literature indicate that the pro-inflammatory response may be impaired in preterm newborns, serum levels of monocyte-derived cytokines, such as TNF-α and IL-6, vary highly between newborns and can reach adult-like concentrations during sepsis. These contradictory observations and the severe consequences of neonatal sepsis in preterm newborns highlight the need for a better understanding of the pro-inflammatory cytokine response of preterm newborns to improve sepsis-related outcomes.Methods and resultsUsing an in vitro model with multiple read outs at the transcriptional and protein level, we consistently showed that the monocyte-derived cytokine response induced by sepsis-related bacteria is comparable between preterm newborns, term newborns and adults. We substantiated these findings by employing recombinant Toll-like receptor (TLR) ligands and showed that the activation of specific immune pathways, including the expression of TLRs, is also similar between preterm newborns, term newborns and adults. Importantly, we showed that at birth the production of TNF-α and IL-6 is highly variable between individuals and independent of gestational age.DiscussionThese findings indicate that preterm newborns are equally capable of mounting a pro-inflammatory response against a broad range of bacterial pathogens that is comparable to term newborns and adults. Our results provide a better understanding of the pro-inflammatory response by preterm newborns and could guide the development of interventions that specifically modulate the pro-inflammatory response during sepsis in preterm newborns.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1353039/fullnewborn – immunologysepsisprematuritybacteriainnate immunitycytokines |
| spellingShingle | Jop Jans Sven C. J. van Dun Renske Gorissen Roel F. A. Pieterman Tess S. Voskamp Sam Schoenmakers Hendrik Robert Taal Wendy W. J. Unger The monocyte-derived cytokine response in whole blood from preterm newborns against sepsis-related bacteria is similar to term newborns and adults Frontiers in Immunology newborn – immunology sepsis prematurity bacteria innate immunity cytokines |
| title | The monocyte-derived cytokine response in whole blood from preterm newborns against sepsis-related bacteria is similar to term newborns and adults |
| title_full | The monocyte-derived cytokine response in whole blood from preterm newborns against sepsis-related bacteria is similar to term newborns and adults |
| title_fullStr | The monocyte-derived cytokine response in whole blood from preterm newborns against sepsis-related bacteria is similar to term newborns and adults |
| title_full_unstemmed | The monocyte-derived cytokine response in whole blood from preterm newborns against sepsis-related bacteria is similar to term newborns and adults |
| title_short | The monocyte-derived cytokine response in whole blood from preterm newborns against sepsis-related bacteria is similar to term newborns and adults |
| title_sort | monocyte derived cytokine response in whole blood from preterm newborns against sepsis related bacteria is similar to term newborns and adults |
| topic | newborn – immunology sepsis prematurity bacteria innate immunity cytokines |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1353039/full |
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