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

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.

Automated summary

Polysialic acid (polySia) is a post-translational modification of cell-surface proteins that plays a role in cellular interactions. In a study using mice deficient in polySia infected with Streptococcus pneumoniae (Spn), it was found that these mice were less susceptible to infection and cleared the bacteria faster. However, their lung infiltration of immune cells was diminished, possibly due to dysregulated signaling. The loss of polySia from migrating immune cells in infected wild-type mice suggests its changing role during an immune response.