Developmental Immaturity of Siglec Receptor Expression on Neonatal Alveolar Macrophages Predisposes to Severe Group B Streptococcal Infection

Summary: Streptococcus agalactiae (Group B Streptococcus, 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 o...

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Main Authors:	Sean J. Lund, Kathryn A. Patras, Jacqueline M. Kimmey, Asami Yamamura, Lindsay D. Butcher, Pamela G.B. Del Rosario, Gilberto E. Hernandez, Alyssa M. McCoy, Omar Lakhdari, Victor Nizet, Lawrence S. Prince
Format:	Article
Language:	English
Published:	Elsevier 2020-06-01
Series:	iScience
Subjects:	Medical Microbiology Reproductive Medicine Microbiome
Online Access:	http://www.sciencedirect.com/science/article/pii/S2589004220303928

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spelling	doaj-08a3b66fdb2f440388d8fc7d11f6b5fb2020-11-25T03:34:52ZengElsevieriScience2589-00422020-06-01236101207Developmental Immaturity of Siglec Receptor Expression on Neonatal Alveolar Macrophages Predisposes to Severe Group B Streptococcal InfectionSean J. Lund0Kathryn A. Patras1Jacqueline M. Kimmey2Asami Yamamura3Lindsay D. Butcher4Pamela G.B. Del Rosario5Gilberto E. Hernandez6Alyssa M. McCoy7Omar Lakhdari8Victor Nizet9Lawrence S. Prince10Department of Pediatrics, University of California, San Diego, Rady Children's Hospital, San Diego, 9500 Gilman Drive, Mail Code 0760, La Jolla, CA 92093-0760, USADepartment of Pediatrics, University of California, San Diego, Rady Children's Hospital, San Diego, 9500 Gilman Drive, Mail Code 0760, La Jolla, CA 92093-0760, USADepartment of Pediatrics, University of California, San Diego, Rady Children's Hospital, San Diego, 9500 Gilman Drive, Mail Code 0760, La Jolla, CA 92093-0760, USADepartment of Pediatrics, University of California, San Diego, Rady Children's Hospital, San Diego, 9500 Gilman Drive, Mail Code 0760, La Jolla, CA 92093-0760, USADepartment of Pediatrics, University of California, San Diego, Rady Children's Hospital, San Diego, 9500 Gilman Drive, Mail Code 0760, La Jolla, CA 92093-0760, USADepartment of Pediatrics, University of California, San Diego, Rady Children's Hospital, San Diego, 9500 Gilman Drive, Mail Code 0760, La Jolla, CA 92093-0760, USADepartment of Pediatrics, University of California, San Diego, Rady Children's Hospital, San Diego, 9500 Gilman Drive, Mail Code 0760, La Jolla, CA 92093-0760, USADepartment of Pediatrics, University of California, San Diego, Rady Children's Hospital, San Diego, 9500 Gilman Drive, Mail Code 0760, La Jolla, CA 92093-0760, USADepartment of Pediatrics, University of California, San Diego, Rady Children's Hospital, San Diego, 9500 Gilman Drive, Mail Code 0760, La Jolla, CA 92093-0760, USADepartment of Pediatrics, University of California, San Diego, Rady Children's Hospital, San Diego, 9500 Gilman Drive, Mail Code 0760, La Jolla, CA 92093-0760, USADepartment of Pediatrics, University of California, San Diego, Rady Children's Hospital, San Diego, 9500 Gilman Drive, Mail Code 0760, La Jolla, CA 92093-0760, USA; Corresponding authorSummary: Streptococcus agalactiae (Group B Streptococcus, 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 in Csf2−/− 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.http://www.sciencedirect.com/science/article/pii/S2589004220303928Medical MicrobiologyReproductive MedicineMicrobiome
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Sean J. Lund Kathryn A. Patras Jacqueline M. Kimmey Asami Yamamura Lindsay D. Butcher Pamela G.B. Del Rosario Gilberto E. Hernandez Alyssa M. McCoy Omar Lakhdari Victor Nizet Lawrence S. Prince
spellingShingle	Sean J. Lund Kathryn A. Patras Jacqueline M. Kimmey Asami Yamamura Lindsay D. Butcher Pamela G.B. Del Rosario Gilberto E. Hernandez Alyssa M. McCoy Omar Lakhdari Victor Nizet Lawrence S. Prince Developmental Immaturity of Siglec Receptor Expression on Neonatal Alveolar Macrophages Predisposes to Severe Group B Streptococcal Infection iScience Medical Microbiology Reproductive Medicine Microbiome
author_facet	Sean J. Lund Kathryn A. Patras Jacqueline M. Kimmey Asami Yamamura Lindsay D. Butcher Pamela G.B. Del Rosario Gilberto E. Hernandez Alyssa M. McCoy Omar Lakhdari Victor Nizet Lawrence S. Prince
author_sort	Sean J. Lund
title	Developmental Immaturity of Siglec Receptor Expression on Neonatal Alveolar Macrophages Predisposes to Severe Group B Streptococcal Infection
title_short	Developmental Immaturity of Siglec Receptor Expression on Neonatal Alveolar Macrophages Predisposes to Severe Group B Streptococcal Infection
title_full	Developmental Immaturity of Siglec Receptor Expression on Neonatal Alveolar Macrophages Predisposes to Severe Group B Streptococcal Infection
title_fullStr	Developmental Immaturity of Siglec Receptor Expression on Neonatal Alveolar Macrophages Predisposes to Severe Group B Streptococcal Infection
title_full_unstemmed	Developmental Immaturity of Siglec Receptor Expression on Neonatal Alveolar Macrophages Predisposes to Severe Group B Streptococcal Infection
title_sort	developmental immaturity of siglec receptor expression on neonatal alveolar macrophages predisposes to severe group b streptococcal infection
publisher	Elsevier
series	iScience
issn	2589-0042
publishDate	2020-06-01
description	Summary: Streptococcus agalactiae (Group B Streptococcus, 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 in Csf2−/− 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.
topic	Medical Microbiology Reproductive Medicine Microbiome
url	http://www.sciencedirect.com/science/article/pii/S2589004220303928
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Developmental Immaturity of Siglec Receptor Expression on Neonatal Alveolar Macrophages Predisposes to Severe Group B Streptococcal Infection

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