Survival and Pulmonary Injury After Neonatal Sepsis: PD1/PDL1's Contributions to Mouse and Human Immunopathology
| Autor: | Eleanor A. Fallon, Monique E. De Paepe, Yaping Chen, Chun-Shiang Chung, Alfred Ayala, Daithi S. Heffernan |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Programmed Cell Death 1 Receptor B7-H1 Antigen sepsis 0302 clinical medicine Immunopathology Immunology and Allergy immunopathology innate immunity Lung Cells Cultured Original Research endothelial cell culture Mice Knockout biology Neonatal sepsis Lung Injury Pulmonary edema Platelet Endothelial Cell Adhesion Molecule-1 medicine.anatomical_structure 030220 oncology & carcinogenesis Myeloperoxidase Female Neonatal Sepsis lcsh:Immunologic diseases. Allergy Immunology Pulmonary Edema Lung injury survival Sepsis neonatal 03 medical and health sciences Immune system medicine Animals Humans business.industry Infant Newborn Endothelial Cells medicine.disease Immunity Innate Mice Inbred C57BL Disease Models Animal 030104 developmental biology programmed cell death receptor Animals Newborn Case-Control Studies biology.protein Zonula Occludens-1 Protein business lcsh:RC581-607 |
| Zdroj: | Frontiers in Immunology, Vol 12 (2021) Frontiers in Immunology |
| ISSN: | 1664-3224 |
| Popis: | Morbidity and mortality associated with neonatal sepsis remains a healthcare crisis. PD1−/− neonatal mice endured experimental sepsis, in the form of cecal slurry (CS), and showed improved rates of survival compared to wildtype (WT) counterparts. End-organ injury, particularly of the lung, contributes to the devastation set forth by neonatal sepsis. PDL1−/− neonatal mice, in contrast to PD1−/− neonatal mice did not have a significant improvement in survival after CS. Because of this, we focused subsequent studies on the impact of PD1 gene deficiency on lung injury. Here, we observed that at 24 h post-CS (but not at 4 or 12 h) there was a marked increase in pulmonary edema (PE), neutrophil influx, myeloperoxidase (MPO) levels, and cytokine expression sham (Sh) WT mice. Regarding pulmonary endothelial cell (EC) adhesion molecule expression, we observed that Zona occludens-1 (ZO-1) within the cell shifted from a membranous location to a peri-nuclear location after CS in WT murine cultured ECs at 24hrs, but remained membranous among PD1−/− lungs. To expand the scope of this inquiry, we investigated human neonatal lung tissue. We observed that the lungs of human newborns exposed to intrauterine infection had significantly higher numbers of PD1+ cells compared to specimens who died from non-infectious causes. Together, these data suggest that PD1/PDL1, a pathway typically thought to govern adaptive immune processes in adult animals, can modulate the largely innate neonatal pulmonary immune response to experimental septic insult. The potential future significance of this area of study includes that PD1/PDL1 checkpoint proteins may be viable therapeutic targets in the septic neonate. |
| Databáze: | OpenAIRE |
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