Infants Younger Than 90 Days Admitted for Late-Onset Sepsis Display a Reduced Abundance of Regulatory T Cells

Objective To provide epidemiological data of infants < 90 days of age with suspected late-onset sepsis (LOS) and evaluate distinct immunological specificities. We hypothesized that previously healthy infants < 3 months of age with sepsis have a yet undefined immunological predisposition; e.g. differences in lymphocyte subsets including regulatory T cells. Methods We performed an exploratory, single center study between January 1(st), 2019 and June 1(st), 2021. Routine diagnostics included conventional culture (blood, cerebrospinal fluid, urine), PCR and inflammatory markers in infants < 90 days of age with suspected sepsis. We additionally analyzed lymphocyte subsets and CD4+ CD25+ forkhead box protein (FoxP3)(+) Tregs at admission for sepsis workup as compared to age-matched controls. Results A convenience sample cohort of n= 51 infants with sepsis workup was enrolled. Invasive bacterial infection (IBI) was diagnosed in 25 (49.0%) patients including two infants with a rhinovirus co-infection and viral infection in 14 (27.5%) neonates. No infectious cause was found in 12 cases. Infants with suspected LOS displayed a decreased abundance of CD4+ FoxP3+ T cells as compared to controls, which was most pronounced in the subgroup of infants with IBI. We also noticed elevated HLA-DR-positive CD3+ cells in infants with LOS and a higher CD4/CD8-ratio in infants with viral infection as compared to healthy controls. Infants with viral infections had a higher number of natural killer cells as compared to infants with IBI. Conclusion Our exploratory data support the concept of a potential immaturity state and failed immune tolerance development for young infants with LOS. Future large-scale studies are needed to elucidate pre-sepsis conditions and to target the microbiome-immunity interplay as a potential risk pattern.

Automated summary

The study found that infants with suspected late-onset sepsis (LOS) had a decreased abundance of CD4+ FoxP3+ T cells compared to controls, especially in those with invasive bacterial infection. Additionally, infants with LOS showed an increase in HLA-DR-positive CD3+ cells, while infants with viral infection had a higher CD4/CD8 ratio than healthy controls.