Macrophage DYRK1A is broadly required for bacterial phagocytosis

Listeria monocytogenes is a foodborne pathogen that can lead to the severe illness listeriosis. Macrophages play a crucial role in the outcome of L. monocytogenes infection, but the specific host factors involved in bacterial uptake have not been fully understood. In a prior genome-wide screen, researchers identified the macrophage kinase DYRK1A as a potential factor influencing L. monocytogenes infection.

Through various approaches, the current study reveals that DYRK1A is essential for efficient internalization of L. monocytogenes by macrophages. It appears to act early in the infection process, primarily by promoting bacterial attachment to the macrophage surface. Genomic analysis of DYRK1A-deficient macrophages shows a reduction in the abundance of genes encoding membrane-associated proteins and components of innate immune and phagocytic pathways, suggesting a transcriptional basis for the observed attachment defect.

The role of DYRK1A extends beyond L. monocytogenes uptake to include the Fc receptor pathway and additional bacterial species across multiple genera, indicating a broad role in macrophage phagocytosis. Together, these findings highlight a previously unrecognized function of the host factor DYRK1A in macrophage phagocytosis, expanding its role beyond its established associations with neurodevelopment and cancer to innate immune defense.