Constitutive TNF-α signaling in neonates is essential for the development of tissue-resident leukocyte profiles at barrier sites
In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Jg. 33 (2019-07-03), Heft 10
Online
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Zugriff:
Newborn infants have a high disposition to develop systemic inflammatory response syndromes (SIRSs) upon inflammatory or infectious challenges. Moreover, there is a considerable trafficking of hematopoietic cells to tissues already under noninflammatory conditions. These age-specific characteristics suggest a hitherto unappreciated crucial role of the vascular endothelium during the neonatal period. Here, we demonstrate that healthy neonates showed already strong endothelial baseline activation, which was mediated by a constitutively increased production of TNF-α. In mice, pharmacological inhibition of TNF-α directly after birth prevented subsequent fatal SIRS but completely abrogated the recruitment of leukocytes to sites of infection. Importantly, in healthy neonates, blocking TNF-α at birth disrupted the physiologic leukocyte trafficking, which resulted in persistently altered leukocyte profiles at barrier sites. Collectively, these data suggest that constitutive TNF-α-mediated sterile endothelial activation in newborn infants contributes to the increased risk of developing SIRS but is needed to ensure the postnatal recruitment of leukocytes to organs and interfaces.-Bickes, M. S., Pirr, S., Heinemann, A. S., Fehlhaber, B., Halle, S., Vollger, L., Willers, M., Richter, M., Bohne, C., Albrecht, M., Langer, M., Pfeifer, S., Jonigk, D., Vieten, G., Ure, B., von Kaisenberg, C., Forster, R., von Kockritz-Blickwede, M., Hansen, G., Viemann, D. Constitutive TNF-α signaling in neonates is essential for the development of tissue-resident leukocyte profiles at barrier sites.
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Constitutive TNF-α signaling in neonates is essential for the development of tissue-resident leukocyte profiles at barrier sites
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Autor/in / Beteiligte Person: | Ure, Benno M. ; Völlger, Lena ; Constantin von Kaisenberg ; Heinemann, Anna S. ; Pirr, Sabine ; Pfeifer, Sandra ; Maren von Köckritz-Blickwede ; Melissa Natalie Langer ; Fehlhaber, Beate ; Viemann, Dorothee ; Marie S Bickes ; Förster, Reinhold ; Richter, Manuela ; Hansen, Gesine ; Jonigk, Danny ; Vieten, Gertrud ; Albrecht, Melanie ; Willers, Maike ; Böhne, Carolin ; Halle, Stephan |
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Zeitschrift: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Jg. 33 (2019-07-03), Heft 10 |
Veröffentlichung: | 2019 |
Medientyp: | unknown |
ISSN: | 1530-6860 (print) |
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