Amplified centrosomes in dendritic cells promote immune cell effector functions

Abstract

Centrosomes constitute structural elements organizing the mitotic spindle in animal cells for proper chromosome segregation. Centrosome numbers are tightly controlled and limited to one during interphase and two before a cell enters mitosis. Defects in regulating centrosome numbers lead to the presence of amplified centrosomes, which are a hallmark of malignant cells and sufficient to induce tumorigenesis. By contrast, amplified centrosomes are rarely observed in normal somatic cells and often removed during terminal differentiation. Here, we demonstrate the presence of amplified centrosomes in dendritic cells (DCs) during immune activation. Mature DCs accumulate centrosomes by mitotic defects and show high expression levels of polo-like kinase 2 (PLK2) leading to over-duplication of centrioles. During cell migration, amplified centrosomes tightly cluster and act as functional microtubule-organizing centers, which promote persistent locomotion. Moreover, DCs with amplified centrosomes show enhanced secretion of inflammatory cytokines and optimized T cell responses. Together, these results demonstrate a previously unappreciated role of amplified centrosomes in promoting the ability of leukocytes to enhance immune responses.