The NimB2 opsonin promotes S. aureus recognition by macrophages in Drosophila melanogaster
TL;DR
The results establish NimB2 as an insect opsonin that links a specific bacterial ligand exposed on the cell envelope to a phagocytic receptor that links a specific bacterial ligand exposed on the cell envelope to a phagocytic receptor.
Abstract
Phagocytosis is a conserved effector process of innate immunity that enables specialized immune cells to detect, engulf, and degrade invading microbes as well as dying cells and cellular debris. Soluble opsonins enhance this process by coating target surfaces and promoting their recognition and uptake by phagocytic cells. In Drosophila, many phagocytic receptors of the Nimrod family have been characterized, but opsonins remain comparatively poorly understood. Here, we identified the secreted Nimrod protein NimB2 as an insect opsonin that specifically promotes the clearance of Staphylococcus aureus bacteria. NimB2 is produced by the fat body, secreted into the hemolymph, and required for resistance to S. aureus infection. NimB2 null mutants showed reduced phagocytosis of S. aureus while maintaining Toll-dependent antimicrobial peptide expression. NimB2 promotes S. aureus binding to plasmatocytes (Drosophila macrophages). Using binding assays and bacterial cell wall mutants, we found that NimB2 recognizes a lipoteichoic acid (LTA)–dependent determinant on the S. aureus surface that allows the coating of the bacterial envelope. We further show that this coating enables efficient recognition by hemocytes via the phagocytic receptor Eater, which is necessary for NimB2-dependent binding. Moreover, Eater overexpression enhances NimB2-mediated association of S. aureus with hemocytes. Together, our results establish NimB2 as an insect opsonin that links a specific bacterial ligand exposed on the cell envelope to a phagocytic receptor.