- Background: Diagnosis of neonatal sepsis is complicated due to limited accuracy of clinical parameters of infection. So-called inflammasomes sense exogen and endogen danger signals thereby effecting the secretion of inflammatory mediators and cell death. We first evaluated the secretion of the inflammasome-dependent alarmins Galectin-1 (Gal-1), progranulin (PGRN) and resistin in septic neonates and examined if surface lipoproteins of Staphylococcus aureus (S. aureus) activate toll-like-receptor 2 (TLR2) for the inflammasome-dependent release of PGRN.
- Methods: The total study population of 78 neonates was divided into an infected (n = 29) and non-infected group (n = 23). 26 newborns were excluded. Blood serum samples and clinical data were evaluated retrospectively. The determination of alarmin levels was performed via ELISA. Moreover, we generated a lipoprotein lipidation deficient S. aureus mutant (ΔLgt S. aureus) via CRISPR/Cas9-mediated base editing. THP1 monocytes were treated with heat-killed wild type S. aureus, ΔLgt S. aureus as well as the synthetic lipoproteins and TLR2 agonists Pam3CSK4 and FSL-1. PGRN and TNF-α release in cell supernatants were detected via ELISA.
- Results: Resistin levels were significantly elevated in infected neonates compared to the non-infected controls. Infected full-term born neonates exhibited higher values of PGRN than non-infected full-term infants. Resistin showed significant elevated concentrations in infected preterm newborns compared to non-infected preterm newborns. The comparison of PGRN and TNF-α release after cell stimulation with bacterial and synthetic lipoproteins showed that PGRN secretion is lipoprotein-dependent and does not require TLR2 activation.
- Conclusion: Only PGRN and resistin emerge as potential sepsis markers in newborns considering their gestational age-dependent secretion. Our findings contribute to uncovering the pathomechanism of Gram-positive infection in newborns.