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

Ingmar Fortmann; Marie-Theres Dammann; Bastian Siller; Alexander Humberg; Martin Demmert; Ludger Tüshaus; Judith Lindert; Vera van Zandbergen; Julia Pagel; Jan Rupp; Egbert Herting; Christoph Härtel

doi:10.3389/fimmu.2021.666447

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

Front Immunol. 2021 Aug 27:12:666447. doi: 10.3389/fimmu.2021.666447. eCollection 2021.

Authors

Ingmar Fortmann^{1

2}, Marie-Theres Dammann¹, Bastian Siller¹, Alexander Humberg¹, Martin Demmert^{1

2}, Ludger Tüshaus³, Judith Lindert³, Vera van Zandbergen¹, Julia Pagel^{1

2}, Jan Rupp^{2

4}, Egbert Herting¹, Christoph Härtel⁵

Affiliations

¹ Department of Pediatrics, University of Lübeck, Lübeck, Germany.
² German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Lübeck, Germany.
³ Department of Pediatric Surgery, University of Lübeck, Lübeck, Germany.
⁴ Department of Infectious Diseases and Microbiology, University of Lübeck, Lübeck, Germany.
⁵ Department of Pediatrics, University Hospital of Würzburg, Würzburg, Germany.

Abstract

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.

Keywords: infants < 90 days; invasive bacterial infection; lymphocyte subsets; neonatal immunity; regulatory T cells; sepsis; sepsis workup.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Age of Onset
Bacterial Infections / microbiology*
Cohort Studies
Communicable Diseases
Female
Forkhead Transcription Factors / blood
Gestational Age
Humans
Immune Tolerance
Infant
Infant, Newborn
Lymphocyte Subsets / cytology
Lymphocyte Subsets / immunology
Male
Sepsis / immunology*
Sepsis / microbiology
T-Lymphocytes, Regulatory / immunology*

Substances

Forkhead Transcription Factors