Sialic Acid-Siglec-E Interactions Regulate the Response of Neonatal Macrophages to Group B Streptococcus.

Autor:	Lund SJ; Department of Pediatrics, University of California, San Diego, La Jolla, CA., Del Rosario PGB; Department of Pediatrics, University of California, San Diego, La Jolla, CA.; Rady Children's Hospital, San Diego, CA., Honda A; Department of Pediatrics, University of California, San Diego, La Jolla, CA., Caoili KJ; Department of Pediatrics, Stanford University, Palo Alto, CA., Hoeksema MA; Department of Medical Biochemistry, Amsterdam University Medical Center, Amsterdam Zuidoost, the Netherlands., Nizet V; Department of Pediatrics, University of California, San Diego, La Jolla, CA., Patras KA; Department of Molecular Virology and Microbiology, Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX., Prince LS; Department of Pediatrics, Stanford University, Palo Alto, CA.
Jazyk:	angličtina
Zdroj:	ImmunoHorizons [Immunohorizons] 2024 May 01; Vol. 8 (5), pp. 384-396.
DOI:	10.4049/immunohorizons.2300076
Abstrakt:	The mammalian Siglec receptor sialoadhesin (Siglec1, CD169) confers innate immunity against the encapsulated pathogen group B Streptococcus (GBS). Newborn lung macrophages have lower expression levels of sialoadhesin at birth compared with the postnatal period, increasing their susceptibility to GBS infection. In this study, we investigate the mechanisms regulating sialoadhesin expression in the newborn mouse lung. In both neonatal and adult mice, GBS lung infection reduced Siglec1 expression, potentially delaying acquisition of immunity in neonates. Suppression of Siglec1 expression required interactions between sialic acid on the GBS capsule and the inhibitory host receptor Siglec-E. The Siglec1 gene contains multiple STAT binding motifs, which could regulate expression of sialoadhesin downstream of innate immune signals. Although GBS infection reduced STAT1 expression in the lungs of wild-type newborn mice, we observed increased numbers of STAT1+ cells in Siglece-/- lungs. To test if innate immune activation could increase sialoadhesin at birth, we first demonstrated that treatment of neonatal lung macrophages ex vivo with inflammatory activators increased sialoadhesin expression. However, overcoming the low sialoadhesin expression at birth using in vivo prenatal exposures or treatments with inflammatory stimuli were not successful. The suppression of sialoadhesin expression by GBS-Siglec-E engagement may therefore contribute to disease pathogenesis in newborns and represent a challenging but potentially appealing therapeutic opportunity to augment immunity at birth. (Copyright © 2024 The Authors.)
Databáze:	MEDLINE
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