Arpin is critical for phagocytosis in macrophages and is targeted by human rhinovirus

Abstract

Human rhinovirus is a causative agent of severe exacerbations of chronic obstructive pulmonary disease (COPD). COPD is characterised by an increased number of alveolar macrophages with diminished phagocytic functions, but how rhinovirus infection affects macrophage function is still unknown. Here, we describe that human rhinovirus 16 impairs bacterial uptake and receptor‐mediated phagocytosis in macrophages. The stalled phagocytic cups contain accumulated F‐actin. Interestingly, we find that human rhinovirus 16 downregulates the expression of Arpin, a negative regulator of the Arp2/3 complex. Importantly, re‐expression of the protein rescues defective internalisation in human rhinovirus 16‐treated cells, demonstrating that Arpin is a key factor targeted to impair phagocytosis. We further show that Arpin is required for efficient uptake of multiple targets, for F‐actin cup formation and for successful phagosome completion in macrophages. Interestingly, Arpin is recruited to sites of membrane extension and phagosome closure. Thus, we identify Arpin as a central actin regulator during phagocytosis that it is targeted by human rhinovirus 16, allowing the virus to perturb bacterial internalisation and phagocytosis in macrophages. image Arpin, the negative regulator of the Arp2/3 complex, plays a key role in phagosome formation. It is downregulated in macrophages infected with human rhinovirus, inducing defects in phagocytosis and bacterial uptake. Arpin is important for efficient phagocytosis and bacterial uptake. Human rhinovirus treated macrophages have impaired phagocytic capacities. Arpin expression is decreased upon rhinovirus infection of macrophages. Arpin targeting by human rhinovirus explains defective internalisation.