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

(Group B , 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 termi...

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Published in:Frontiers in immunology Vol. 14; p. 1268804
Main Authors: Ravi, Denho, Ntinopoulou, Erato, Guetta, Nessim, Weier, Manuela, Vogel, Verena, Spellerberg, Barbara, Sendi, Parham, Gremlich, Sandrine, Roger, Thierry, Giannoni, Eric
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 14.11.2023
Subjects:
Adult
cytokine
group B streptococcus
Humans
Immunology
Infant, Newborn
innate immunity
Interleukin-10
Interleukin-12
Interleukin-23
Interleukin-6
macrophage
Macrophage Colony-Stimulating Factor
Macrophages
Neonatal Sepsis
newborn
phagocytosis
Streptococcus agalactiae
cytokine
group B streptococcus
phagocytosis
streptococcus agalactiae
innate immunity
macrophage
newborn
ISSN:1664-3224, 1664-3224
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Summary:(Group B , 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. 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. 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. 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.
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ORCID: Barbara Spellerberg, orcid.org/0000-0001-7552-8764; Parham Sendi, orcid.org/0000-0002-7347-6312; Thierry Roger, orcid.org/0000-0002-9358-0109; Eric Giannoni, orcid.org/0000-0003-0897-6529
Edited by: Joseph Alex Duncan, University of North Carolina at Chapel Hill, United States
Reviewed by: Wendy W. J. Unger, Erasmus Medical Center, Netherlands; Asmaa Tazi, INSERM U1016 Institut Cochin, France; Pascal M. Lavoie, University of British Columbia, Canada
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2023.1268804