Polysialylation controls immune function of myeloid cells in murine model of pneumococcal pneumonia

Prajakta Shinde; Alexander Kiepas; Lei Zhang; Shreya Sudhir; Konstantinos Konstantopoulos; Nicholas M Stamatos

doi:10.1016/j.celrep.2023.112648

Polysialylation controls immune function of myeloid cells in murine model of pneumococcal pneumonia

Cell Rep. 2023 Jun 27;42(6):112648. doi: 10.1016/j.celrep.2023.112648. Epub 2023 Jun 19.

Authors

Prajakta Shinde¹, Alexander Kiepas², Lei Zhang¹, Shreya Sudhir¹, Konstantinos Konstantopoulos², Nicholas M Stamatos³

Affiliations

¹ Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
² Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
³ Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: nstamatos@ihv.umaryland.edu.

Abstract

Polysialic acid (polySia) is a post-translational modification of a select group of cell-surface proteins that guides cellular interactions. As the overall impact of changes in expression of this glycan on leukocytes during infection is not known, we evaluate the immune response of polySia-deficient ST8SiaIV^-/- mice infected with Streptococcus pneumoniae (Spn). Compared with wild-type (WT) mice, ST8SiaIV^-/- mice are less susceptible to infection and clear Spn from airways faster, with alveolar macrophages demonstrating greater viability and phagocytic activity. Leukocyte pulmonary recruitment, paradoxically, is diminished in infected ST8SiaIV^-/- mice, corroborated by adoptive cell transfer, microfluidic migration experiments, and intravital microscopy, and possibly explained by dysregulated ERK1/2 signaling. PolySia is progressively lost from neutrophils and monocytes migrating from bone marrow to alveoli in Spn-infected WT mice, consistent with changing cellular functions. These data highlight multidimensional effects of polySia on leukocytes during an immune response and suggest therapeutic interventions for optimizing immunity.

Keywords: CP: Immunology; Streptococcus pneumoniae; extracellular signal-regulated kinase ERK1/2; intravital microscopy; leukocyte migration; microfluidic migration chambers; monocytes; neutrophils; phagocytosis; polysialic acid; polysialyltransferase ST8SiaIV.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Animals
Disease Models, Animal
Immunity
Mice
Myeloid Cells / metabolism
Pneumonia, Pneumococcal*
Sialic Acids / metabolism
Streptococcus pneumoniae / metabolism

Substances

polysialic acid
Sialic Acids

Abstract

Publication types

MeSH terms

Substances

Grants and funding