Dysregulated monocyte-derived macrophage response to Group B Streptococcus in newborns

Denho Ravi; Erato Ntinopoulou; Nessim Guetta; Manuela Weier; Verena Vogel; Barbara Spellerberg; Parham Sendi; Sandrine Gremlich; Thierry Roger; Eric Giannoni

doi:10.3389/fimmu.2023.1268804

Dysregulated monocyte-derived macrophage response to Group B Streptococcus in newborns

Front Immunol. 2023 Nov 14:14:1268804. doi: 10.3389/fimmu.2023.1268804. eCollection 2023.

Authors

Denho Ravi^{1

2}, Erato Ntinopoulou^{1

2}, Nessim Guetta^{1

2}, Manuela Weier^{1

2}, Verena Vogel³, Barbara Spellerberg³, Parham Sendi⁴, Sandrine Gremlich^{1

2}, Thierry Roger², Eric Giannoni^{1

2}

Affiliations

¹ Clinic of Neonatology, Department Mother-Woman-Child, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
² Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
³ Institute of Medical Microbiology and Hygiene, University of Ulm, Ulm, Germany.
⁴ Institute for Infectious Diseases, University of Bern, Bern, Switzerland.

Abstract

Introduction: Streptococcus agalactiae (Group B Streptococcus, GBS) is a leading pathogen of neonatal sepsis. The host-pathogen interactions underlying the progression to life-threatening infection in newborns are incompletely understood. Macrophages are first line in host defenses against GBS, contributing to the initiation, amplification, and termination of immune responses. The goal of this study was to compare the response of newborn and adult monocyte-derived macrophages (MDMs) to GBS.

Methods: Monocytes from umbilical cord blood of healthy term newborns and from peripheral blood of healthy adult subjects were cultured with M-CSF to induce MDMs. M-CSF-MDMs, GM-CSF- and IFNγ-activated MDMs were exposed to GBS COH1, a reference strain for neonatal sepsis.

Results: GBS induced a greater release of IL-1β, IL-6, IL-10, IL-12p70 and IL-23 in newborn compared to adult MDMs, while IL-18, IL-21, IL-22, TNF, RANTES/CCL5, MCP-1/CCL2 and IL-8/CXCL8 were released at similar levels. MDM responses to GBS were strongly influenced by conditions of activation and were distinct from those to synthetic bacterial lipopeptides and lipopolysaccharides. Under similar conditions of opsonization, newborn MDMs phagocytosed and killed GBS as efficiently as adult MDMs.

Discussion: Altogether, the production of excessive levels of Th1- (IL-12p70), Th17-related (IL-1β, IL-6, IL-23) and anti-inflammatory (IL-10) cytokines is consistent with a dysregulated response to GBS in newborns. The high responsiveness of newborn MDMs may play a role in the progression of GBS infection in newborns, possibly contributing to the development of life-threatening organ dysfunction.

Keywords: cytokine; group B streptococcus; innate immunity; macrophage; newborn; phagocytosis; streptococcus agalactiae.

Publication types

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

MeSH terms

Adult
Humans
Infant, Newborn
Interleukin-10*
Interleukin-12
Interleukin-23
Interleukin-6
Macrophage Colony-Stimulating Factor
Macrophages
Neonatal Sepsis*
Streptococcus agalactiae

Substances

Interleukin-10
Macrophage Colony-Stimulating Factor
Interleukin-6
Interleukin-12
Interleukin-23

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Swiss National Science Foundation (grant #320030_197618 to EG, grant #310030_207418 to TR), the WEGH Foundation (to EG), and by a grant from the European Society for Pediatric Research (to EG). EN was supported by a Swiss Government Excellence Research Scholarship.