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


ABSTRACT: 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 (???) 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. ??? depletion and disruption of ??? differentiation in Csf2-/- mice both impaired GBS clearance. AM? engage the heavily sialylated GBS capsule via the cell surface Siglec receptors Sn and Siglec-E. Although both newborn and adult ??? expressed Siglec-E, newborn ??? expressed significantly lower levels of Sn. We propose that a developmental delay in Sn expression on ??? may prevent effective killing and clearing of GBS from the newborn lung.

SUBMITTER: Lund SJ 

PROVIDER: S-EPMC7300150 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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

Lund Sean J SJ   Patras Kathryn A KA   Kimmey Jacqueline M JM   Yamamura Asami A   Butcher Lindsay D LD   Del Rosario Pamela G B PGB   Hernandez Gilberto E GE   McCoy Alyssa M AM   Lakhdari Omar O   Nizet Victor V   Prince Lawrence S LS  

iScience 20200528 6


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 additi  ...[more]

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