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标题：Developmental Immaturity of Siglec Receptor Expression on Neonatal Alveolar Macrophages Predisposes to Severe Group B Streptococcal Infection
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作者：Sean J. Lund ; Kathryn A. Patras ; Jacqueline M. Kimmey 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：6
页码：1-22
DOI：10.1016/j.isci.2020.101207
语种：English
出版社：Elsevier
摘要：SummaryStreptococcus agalactiae(Group BStreptococcus, GBS) is the most common neonatal pathogen. However, the cellular and molecular mechanisms for neonatal susceptibility to GBS pneumonia and sepsis are incompletely understood. Here we optimized a mouse model of GBS pneumonia to test the role of alveolar macrophage (ΑΜΦ) maturation in host vulnerability to disease. Compared with juvenile and adult mice, neonatal mice infected with GBS had increased mortality and persistence of lung injury. In addition, neonatal mice were defective in GBS phagocytosis and killing. ΑΜΦ depletion and disruption of ΑΜΦ differentiation inCsf2−/−mice both impaired GBS clearance. AMΦ engage the heavily sialylated GBS capsule via the cell surface Siglec receptors Sn and Siglec-E. Although both newborn and adult ΑΜΦ expressed Siglec-E, newborn ΑΜΦ expressed significantly lower levels of Sn. We propose that a developmental delay in Sn expression on ΑΜΦ may prevent effective killing and clearing of GBS from the newborn lung.Graphical AbstractDisplay OmittedHighlights•Newborn mice fail to kill GBS, developing persistent lung injury•Mature AMΦ detect the Sialic acid capsule on GBS to mediate bacterial clearance•Immature newborn AMΦ lack mature Siglec expression required for killing GBS•GBS engages the inhibitory Siglec-E on newborn AMΦ to suppress innate immunityMedical Microbiology; Reproductive Medicine; Microbiome