Developmental Immaturity of Siglec Receptor Expression on Neonatal Alveolar Macrophages Predisposes to Severe Group B Streptococcal Infection
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
Affiliations
Sean J. Lund
Department 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
Kathryn A. Patras
Department 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
Jacqueline M. Kimmey
Department 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
Asami Yamamura
Department 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
Lindsay D. Butcher
Department 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
Pamela G.B. Del Rosario
Department 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
Gilberto E. Hernandez
Department 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
Alyssa M. McCoy
Department 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
Omar Lakhdari
Department 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
Victor Nizet
Department 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
Lawrence S. Prince
Department 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 author
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.
