Actin assembly-inducing protein ActA promotes FcγRIa-mediated Listeria internalization

Listeria monocytogenes is a Gram-positive intracellular pathogen and the causative agent of human listeriosis. While the ability of L. monocytogenes to enter and survive in professional phagocytes is critical to establish a successful infection, mechanisms of invasion are poorly understood. Our previous investigation into the role of type I interferon-stimulated genes in bacterial infection revealed that the human immunoglobulin receptor FcγRIa served as a L. monocytogenes invasion factor. FcγRIa-mediated L. monocytogenes entry occurred independently of immunoglobulin interaction or bacterial internalins. However, the bacterial determinants that mediate FcγRIa interaction remain unclear. Using a comparative genomics approach, we identify actin assembly-inducing protein ActA as a pathogen specific ligand of FcγRIa. FcγRIa enhanced entry of pathogenic L. monocytogenes and L. ivanovii strain but not non-pathogenic L. innocua . We found that the major virulence regulator PrfA is required for pathogen entry into FcγRIa-expressing cells and identify its gene target actA as the critical Listeria ligand. ActA alone was sufficient to promote entry into FcγRIa-expressing cells, and this function is independent of its actin nucleating activity. Together, these studies present an unexpected role of ActA beyond its canonical function in actin-based motility and expand our understanding of Listeria strategies for host cell invasion.